Tetrahydrocarbazol derivatives as ligands for G-protein-coupled receptors (GPCR) | Patent Publication Number 20030232873

US 20030232873 A1

Application Number10319833

Filled DateDec 16, 2002

Priority DateDec 21, 2001

Publication DateDec 18, 2003

Original AssigneeZentaris Ag

Inventor/ApplicantsKlaus Wolfgang Paulini
Hans Peter Muhn
Kenneth Jay Shaw
Marcus Karl Koppitz
Kenneth Jay Shaw
Marcus Karl Koppitz
Hans Peter Muhn
Holger Hess-Stump
Holger Hess-Stumpp
Klaus Paulini

International

A61K

C07D

National

548/448

514/339

548/444.

514/411.

514/411

548/439

546/276.7

Field of Search

This invention provides new tetrahydrocarbazole derivatives that act as ligands for G-protein-coupled receptors (GPCR), especially as antagonists of the gonadotropin-releasing hormone (GnRH). A pharmaceutical composition that contains these new tetrahydrocarbazole derivatives as well as a process for the production of the new tetrahydrocarbazole derivatives are also provided. Moreover, this invention relates to the administration of tetrahydrocarbazole derivatives for treating pathologic conditions that are mediated by GPCR, especially for inhibiting GnRH, in mammals, especially humans, who require such an administration, as well as the use of tetrahydrocarbazole derivatives for the production of a pharmaceutical agent for treating GPCR-mediated pathologic conditions, especially for inhibiting GnRH.

1. Compound of general formula (I)
4. Compound according to one of claims 1 to 3, whereby radicals R2, R3, R4 and/or R5 are not hydrogen atoms.
7. Compound according to one of claims 1 to 5, whereby radical R6 is a hydrophobic radical that comprises alkyl, aryl and/or hetaryl structures and that carries a hydrogen bridge-donor-acceptor system at a distance of two to four single bonds, counting from the carbon atoms that are substituted by radicals R6 and R7.
10. Compound according to one of claims 1 to 5, 7 or 8, whereby radical R is a hydrophobic radical that comprises alkyl, aryl and/or hetaryl structures.
13. Compound according to one of claims 1 to 5, 7, 8, 10 or 11, whereby the compound is present on the carbon atom in R-configuration that is substituted by radicals R6 and R7, if radicals R6 and R7 together form an alpha-aminocarboxylic acid structural element.
15. Pharmaceutical composition that comprises at least one compound according to one of claims 1 to 14.
18. Process for the production of a compound according to one of claims 1 to 14.
19. Compound according to one of claims 1 to 14, for use as a pharmaceutical agent.
20. Use of a compound according to one of claims 1 to 14, for the production of a pharmaceutical agent for treating pathologic conditions that are mediated by G-protein-coupled receptors.

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0001 This application claims the benefit of the filing date of U.S. Provisional Application Serial No. 60/341,878 filed Dec. 21, 2001.

0002 This invention relates to new tetrahydrocarbazole derivatives, the ligands of G-protein-coupled receptors, and especially antagonists of the gonadotropin-releasing hormone, their production, their use as well as pharmaceutical compositions that comprise these tetrahydrocarbazole derivatives. This invention also relates to a process for treating pathologic conditions that are mediated by G-protein-coupled receptors in a mammal, especially a human.

TECHNICAL BACKGROUND 0003 The structural element that is common to all members of the family of the G-protein-coupled receptors (GPCR) is the presence of seven transmembrane-alpha-helical segments that are connected to one another by alternating intracellular and extracellular loops, whereby the amino-terminus is found on the extracellular side, and the carboxy-terminus is found on the intracellular side. The family of GPCRs can be divided into several subfamilies (essentially families A, B and C) with additional sequence homologies within these subfamilies. Since GPCRs are involved primarily in signal reception and transmission, a number of physiological functions are influenced by them. GPCR ligands are therefore potentially suitable as medications for therapy and prevention of a large number of pathologic conditions. A small overview on diseases that can be treated with GPCR ligands is provided in Table I in S. Wilson et al., Pharmaceutical News 2000, 7(3). 0004 The majority of known GPCR ligands are of peptidic structure. Peptidic receptor ligands, however, often have some significant drawbacks, such as, for example, low bioavailability and metabolic instability. Therefore, in recent years, an intensified search has been run for ligands in the form of small, non-peptidic molecules. So-called privileged structures play a special role in the search for new, non-peptidic receptor ligands. These privileged structures are those basic molecular structures that prepare ligands for a number of different receptors. The term privileged structures was used for the first time by Evans et al. in connection with the benzodiazepine-based CCK (cholecystokinin)-A antagonists from the natural substance Asperlicin (B. E. Evans et al., J. Med. Chem. 1988, 31, 2235). For proteases, it has already been known for a long time, for example, that certain structure classes can be used as inhibitors for various enzymes. While in the past primarily mechanism-based inhibitors were described for various proteases, more recently, however, and more and more often, examples of compounds that readily fit into the active binding regions of various enzymes because of their three-dimensional structure have been found (cf. M. Whittaker, Cur. Opin. Chem. Biol. 1998, 2, 386; A. S. Ripka et al., ibid., 441). Such privileged structures were also already described for GPCRs. Examples to this end, in addition to the above-mentioned benzodiazepines, are also peptoids, 4-substituted 4-arylpiperidines, but also special -Turn mimetic agents that are made rigid (B. A. Bunin et al., Ann. Rep. Med. Chem. 1999, 34, 267; R. N. Zuckermann et al., J. Med. Chem. 1994, 37, 2678; G. C B. Harriman, Tetrahedron Lett. 2000, 41, 8853). A survey to this end is found in A. A. Patchett et al., Ann. Rep. Med. Chem. 1999, 35, 289. With the tetrahydrocarbazole derivatives according to this invention, another class of privileged structures is made available for GPCRs. 0005 Although this invention generally prepares ligands for GPCRs, the compounds that are prepared by this invention are especially suitable as ligands for a certain representative of the class of GPCRs, namely the gonadotropin-releasing hormone (GnRH). The GnRH can be classified in subfamily A of the GPCRs (cf. U. Gether et al., Endocrine Reviews 2000, 21(1), 90). 0006 GnRH is a hormone that mainly, but not exclusively, is synthesized in mammals by the nerve cells of the hypothalamus, is transported via the portal veins into the pituitary gland and is released in a regulated manner to the gonadotropic cells. By interaction with its receptor that has seven transmembrane domains, GnRH stimulates the production and the release of gonadotropic hormones by means of the second messenger inositol-1,4,5-triphosphate and Ca2 ions. The gonadotropin-luteinizing hormone (LH) that is released by GnRH and the follicle-stimulating hormone (FSH) stimulate the production of sex steroids and the gamete maturation in both sexes. In addition to GnRH (also referred to as GnRH1), there are two other forms of GnRH, namely GnRH2 and 3. 0007 The GnRH receptor is used as a pharmacological target in a number of diseases, which are dependent on a functioning sex hormone production, for example prostate cancer, premenopausal breast cancer, endometriosis and uterine fibroids. In the case of these diseases, GnRH superagonists or GnRH antagonists can be used successfully. In particular, the male birth control in combination with a substitution dose of androgens forms a possible further indication. 0008 An advantage of GnRH antagonists in comparison to GnRH superagonists is their immediate effectiveness in the blocking of the gonadotropin secretion. Superagonists initially produce an overstimulation of the hypophysis, which results in increased gonadotropin and sex steroid releases. This hormonal reaction is only completed after a certain delay based on the desensitization and downward-adjustment of the GnRH receptor concentrations. Therefore, GnRH superagonists, both alone and in combination with testosterone, may not be able to suppress sperm production in males effectively and thus are not suitable for male birth control. In contrast to this, peptidic GnRH antagonists, especially in combination with a substitution dose of androgen, are able to bring about a significant oligozoospermia in humans. 0009 Peptidic GnRH antagonists, however, have a number of drawbacks. They have a considerably lower effectiveness as superagonists and consequently have to be administered at considerably higher dosages. Their oral bio-availability is also low, so that they have to be administered by injection. Repeated injections lead in turn to a reduction in compliance. Moreover, the synthesis of peptidic GnRH antagonists in comparison to non-peptidic compounds is costly and labor-intensive. 0010 Quinoline derivatives as non-peptidic GnRH antagonists are disclosed in, for example, WO 97/14682. To date, however, it was not possible to market any non-peptidic GnRH antagonists.

TECHNICAL OBJECT 0011 The object on which this invention is based consists in providing new compounds that are suitable for treatment of pathologic conditions that are mediated by GPCR and that have in particular a GnRH-inhibiting (GnRH-antagonistic) action. The new GPCR ligands, preferably GnRH antagonists, should as much as possible be superior to the known peptide compounds and represent an effective alternative or improvement relative to known non-peptidic compounds. The new GPCR ligands, especially GnRH antagonists, are to have primarily high effectiveness and as high an oral bio-availability as possible. In addition, they should be able to be synthesized simply and with as low costs as possible. Pharmaceutical compositions that contain the new non-peptidic GPCR compounds, especially GnRH antagonists, are also provided by this invention. 0012 Another object on which this invention is based is the provision of new GPCR ligands, preferably GnRH antagonists, for use as pharmaceutical agents or for use for the production of pharmaceutical agents that comprise the GPCR ligands, preferably GnRH antagonists. 0013 Moreover, an object of this invention is to provide a process for treating pathologic conditions that are mediated by GPCR, especially for inhibiting GnRH, in a mammal, especially a human. 0014 All of these objects are achieved in a surprising way by the provision of new tetrahydrocarbazole derivatives, the pharmaceutical compositions that contain these tetrahydrocarbazole derivatives, the process for the production of these tetrahydrocarbazole derivatives as well as the process for treating pathologic conditions that are mediated by GPCR, preferably for inhibiting GnRH, in a mammal, especially a human, by administering the tetrahydrocarbazole derivatives or the use of the tetrahydrocarbazole derivatives for the production of pharmaceutical agents for treating pathologic conditions that are mediated by GPCR, especially for GnRH inhibition.

SUMMARY OF THE INVENTION 0015 In a first aspect, this invention provides new tetrahydrocarbazole derivatives of general formula (I). 0016 In a second aspect, pharmaceutical compositions are provided that comprise at least one of the new tetrahydrocarbazole derivatives of general formula (I). 0017 In a third aspect, this invention provides tetrahydrocarbazole derivatives of general formula (I) for use as pharmaceutical agents. 0018 In another aspect, this invention relates to the use of a tetrahydrocarbazole derivative of general formula (I) for the production of a pharmaceutical agent for treating pathologic conditions that are mediated by GPCR, especially for inhibiting the GnRH. This invention also relates to a process for treating pathologic conditions that are mediated by GPCR, especially for inhibiting GnRH in a mammal, preferably a human, whereby an effective amount of a compound of general formula (I) according to the invention is administered to a mammal, preferably a human, who requires such a treatment. 0019 In addition, this invention provides a process for the production of tetrahydrocarbazole derivatives of general formula (I). This process comprises, for example, the steps of condensation of a cyclohexanone derivative that is anchored to a solid phase and suitably substituted with a suitably substituted phenylhydrazine derivative, a subsequent derivatization depending on the desired structure of the final compound and finally cleavage from the solid phase and isolation of the product.

DETAILED DESCRIPTION OF THE INVENTION 0020 In a first aspect of this invention, new tetrahydrocarbazole compounds of general formula (I) 1

0021 are provided, in which 0022 radical R1 is a hydrogen atom, a C2-C6 alkenyl radical or a C1-C6 alkyl radical, and can optionally be substituted with an aryl radical, hetaryl radical or the group COOR11, whereby the aryl or hetaryl radical can be substituted with up to three substituents, which are selected independently of one another from the group that consists of NO2, CH3, CF3, OCH3, OCF3 and halogen atoms, and 0023 radical R11 is a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 aralkyl radical, an aryl radical, a hetaryl radical or the group COCH3, and optionally can be substituted with a substituent that is selected from the group that consists of CONH2, COCH3, COOCH3, SO2CH3 and aryl radicals; 0024 radicals R2, R3, R4 and R5, independently of one another, in each case are a hydrogen atom, a halogen atom, the group COOH, CONH2, CF3, OCF3, NO2, CN, a C1-C6 alkyl radical, a C1-C6 alkenyl radical, a C1-C6 alkoxy radical, a C1-C12 aralkyl radical, an aryl or hetaryl radical; 0025 radical R6 is the group CONR8R9, COOR8, CH21NR8R9, CH2R8, CH2OR8 or a C1-C12 alkenyl radical, which optionally is substituted with radicals R8 and R9, 0026 whereby radicals R8 and R9, independently of one another, in each case are a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 aralkyl radical, a C1-C12 hetaralkyl radical, an aryl radical or hetaryl radical, which can be substituted with one or more substituents, which are selected from the group that consists of OH, NH2, CONHR10, COOR10, NHC(NH)NH2 and halogen atoms, 0027 whereby radical R10 is a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 aralkyl radical, an aryl radical or hetaryl radical, and optionally is substituted with the group CON(R11)2, 0028 or whereby radicals R8 and R9 together can form a ring structure that either consists exclusively of carbon atoms or, in mixed form, consists of carbon atoms and heteroatoms; 0029 radical R7 is a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 alkenyl radical, a C1-C12 aralkyl radical, an aryl radical or a hetaryl radical, the group NR12 R13, NHCOR14, NHCONHR14, NHCOOR4 or NHSO2R14, and optionally can be substituted with one or more substituents, which are selected from the group that consists of OH, NH2, CONH2, COOH and halogen atoms, 0030 radicals R12 and R13, independently of one another, in each case are a hydrogen atom, a C2-C6 alkenyl radical or a C1-C12 alkyl radical and optionally can be substituted with one or more aryl or hetaryl radicals, which in turn can be substituted with up to three substituents, which independently of one another are selected from the group that consists of NO2, CH3, CF3, OCH3, OCF3 and halogen atoms, and radical R4 is a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 alkenyl radical, a C1-C12 aralkyl radical, an aryl radical or a hetaryl radical, which optionally can be substituted with one or more substituents, which are selected from the group that consists of NO2, CH3, OR11, CF3, OCF3, OH, N(R11)2, OCOR11, COOH, CONH2, NHCONHR11, NHCOOR11 and halogen atoms; 0031 and radicals Ra, Rb, Rc, Rd, Re and Rf, independently of one another, in each case are a hydrogen atom, a halogen atom, the group COOH, CONH2, CF3, OCF3, NO2, CN, a C1-C6 alkyl radical, C1-C6 alkoxy radical, an aryl radical or a hetaryl radical; 0032 provided that the compound of general formula (I) is not selected from the group that consists of 3-amino-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, 3-amino-6-methoxy-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, 3-amino-6-benzyloxy-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, methyl-3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate, ()-menthyl-3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate or 3-tert-butoxycarbonyl-amino-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid. 0033 Compounds of general formula (I) as indicated above with all meanings for the radicals that are contained in (I) that are indicated above are an embodiment of the invention, whereby radical R11 is a heteroalkyl radical or a hetaryalkyl radical. 0034 The basic tetrahydrocarbazole structures of the compounds that are excluded by name above from the compounds that fall under the definition of general formula (I) were presented by Y. Maki et al. in Chem. Pharm. Bull. 1973, 21 (11), 2460-2465 as well as by R. Millet et al. in Letters in Peptide Science 1999, 6, 221-233. 0035 The terms that are indicated to explain the compounds of general formula (I) have in particular the following meaning: 0036 C1-C6 or C1-C12 alkyl radical is defined as a branched or unbranched, cyclic or noncyclic, optionally substituted alkyl group with 1 to 6 or 1 to 12 carbon atoms. Representative examples of such alkyl groups include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, n-pentyl, 2,2-dimethylpropyl, 3-methylbutyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl and n-dodecyl groups as well as cyclic groups, especially cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl groups, 1-cyclopropyl, 1-cyclobutyl, 1-cyclopentyl, 1-cyclohexyl, 1-cycloheptylethyl, 2-cyclopropyl, 2-cyclobutyl, 2-cyclopentyl, 2-cyclohexyl, 2-cycloheptylethyl groups and the like, but they are not limited to the latter. 0037 C2-C6 Alkenyl radical is defined as a branched or unbranched, cyclic or non-cyclic, unsaturated alkenyl group, optionally substituted in one or more places, with 2 to 6 carbon atoms. Representative examples of such alkenyl groups include vinyl, allyl, prop-1-enyl, but-1-enyl, but-2-enyl, but-3-enyl, buta-1,3-dienyl, pent-1-enyl, pent-2-enyl, pent-3-enyl, pent-4-enyt, penta-1,3-dienyl, penta-1,4-dienyl, penta-2,3-dienyl, isoprenyl, hex-1-enyl, hex-2-enyl, hex-3-enyl, hex-4-enyl, hex-5-enyl, hexa-1,3-dienyl, hexa-1,4-dienyl, hexa-1,5-dienyl, hexa-2,4-dienyl, hexa-2,5-dienyl, hexa-1,4-dienyl, hexa-1,3,5-trienyl groups and the like, but they are not limited to the latter. 0038 C2-C6 Alkoxy radical is defined as a branched or unbranched, cyclic or non-cyclic, optionally substituted alkoxy group with 2 to 6 carbon atoms. Representative examples of such alkoxy groups include methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, tert-butoxy, n-pentoxy, n-hexoxy, cyclohexyloxy groups and the like, but they are not limited to the latter. 0039 C1-C12 Aralkyl radical is defined as an alkyl radical with 1 to 12 carbon atoms that is substituted by one or more aryl radicals. Representative examples of such aralkyl groups for the purposes of this invention include benzyl, 1-phenylethyl, 1-phenylpropyl, 1-phenylbutyl, 1-phenylhexyl, 1-phenyl-2-methylethyl, 1-phenyl-2-ethylethyl, 1-phenyl-2,2-dimethylethyl, benzhydryl, triphenylmethyl, 2- or 3-naphthylmethyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl groups and the like, but they are not limited to the latter. Accordingly, a hetaralkyl radical is an alkyl radical that is substituted by a heteroaryl radical. 0040 Aryl radical is defined as an optionally substituted monocyclic or polycyclic aromatic group. Representative examples of such aryl groups include phenyl groups, naphthyl groups, and the like, but they are not limited to the latter. 0041 The designation hetaryl radical is identical to the designation heteroaryl radical and stands for an aryl group, as defined above, that in the structure thereof comprises one or more heteroatoms, in particular nitrogen, phosphorus, oxygen, sulfur and arsenic atoms. Representative examples of such hetaryl or heteroaryl groups include unsubstituted hetaryl radicals as well as substituted hetaryl radicals, in particular imidazolyl, pyridyl, quinolinyl groups and the like, but they are not limited to the latter. 0042 The designation ring structure comprises optionally substituted monocyclic or polycyclic ring structures with a different number of ring members, but in particular five-, six- and seven-membered ring structures. In these ring structures, in addition to carbon atoms, one or more heteroatoms, such as in particular nitrogen, phosphorus, oxygen, sulfur and arsenic atoms, can also be included. The ring structures can comprise saturated, but also partially or completely unsaturated, structural elements. Representative examples of such ring structures include aza, oxa, thia, phosphacyclopentane, phosphacyclohexane, phosphacycloheptane, diaza, dioxa, dithia, diphosphacyclopentane, diphosphacyclohexane, and diphosphacycloheptane basic ring structures and the like, as well as basic ring structures with mixed heteroatom exchange, but they are not limited to the latter. 0043 Halogen atoms comprise in particular fluorine, chlorine, bromine and iodine atoms, especially preferably chlorine atoms. 0044 At this point, it can also be pointed out that in addition to the compounds of general formula (I) that are mentioned in the art, as defined above, physiologically compatible derivatives or analogs, in particular also salts of these compounds are also included by this invention. 0045 In addition, it can be noted at this point that the designation receptor ligand or ligand for the purposes of this invention is to designate any compound that binds in any way to a receptor (in this invention, the receptor is a GPCR receptor, preferably a GnRH receptor) and triggers either an activation, an inhibition or other conceivable action in the case of this receptor. The term ligand thus comprises agonists, antagonists, partial agonists/antagonists and other ligands that cause an action in the reactor that is similar to the action of agonists, antagonists or partial agonists/antagonists. The compounds of general formula (I) according to the invention are preferably antagonists of the GnRH. 0046 New tetrahydrocarbazole derivatives of general formula (I) according to the invention, in which radical R7 is not a hydrogen atom, if radical R6 is simultaneously an alkyl radical, are an embodiment of this invention. 0047 Compounds of general formula (I) in which radical R7 is not a hydrogen atom in any case are another embodiment of this invention. 0048 Preferred new tetrahydrocarbazole derivatives of general formula (I) according to the invention are any compounds in which the radicals Ra, Rb, Rc, Rd, Re and Rf are hydrogen atoms. 0049 Also preferred new tetrahydrocarbazole derivatives of general formula (I) according to the invention are any compounds in which radical R1 is a hydrogen atom. 0050 Preferred new tetrahydrocarbazole derivatives of general formula (I) according to the invention are in addition any compounds in which radicals R2, R3, R4 and/or R5 are not hydrogen atoms. Especially preferred in this case are any compounds of general formula (I) in which radicals R2, R3, R4 and R5, independently of one another, are methyl, chloro or methoxy radicals. Quite especially preferred in this case are any compounds of general formula (I) in which at least radical R2 is not a hydrogen atom, especially the compounds 0051 Phenylmethyl-(1S,2S)-1-(3R)-3-(1S)-1-(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-8-methyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate (compound No. 150a in the examples), 0052 Phenylmethyl-(1S,2S)-1-(3R)-3-(1S)-1-(aminocarbonyl)--methylpropylamino-carbonyl-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamate (148a), 0053 Phenylmethyl-(1S,2S)-1-(3R)-3-(1S)-1-(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-8-methoxy-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate (147a). 0054 Preferred new tetrahydrocarbazole derivatives of general formula (I) according to the invention are also any compounds in which R6 is a hydrophobic radical that comprises alkyl, aryl and/or hetaryl structures and that carries a hydrogen bridge-donor-acceptor system at a distance of two to four single bonds, counting from the carbon atoms that are substituted by radicals R6 and R7. Especially preferred are compounds of general formula (I), whereby radical R6 is: 0055 a phenylalanylamide radical, in particular the compound phenylmethyl-(1S,2S)-1-(3R)-3-(1S)-2-amino-2-oxo-1-(phenylmethyl)ethyl-aminocarbony-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-m-ethylbutylcarbamate (66), 0056 an isoleucylamide radical, in particular the compound phenylmethyl (1S,2S)-1-(3R)-3-(1S,2S)-1-(aminocarbonyl)-2-methylbutylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate (64), 0057 a valyl-4-aminobenzoic acid amide radical, in particular the compound phenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-4-(aminocarbonyl)phenylamino-carbonyl-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate (45), 0058 a valyl-N-methylamide radical, in particular the compound phenylmethyl (1S,2S)-2-methyl-1-(3R)-2,3,4,9-tetrahydro-3-(1S)-2-methyl-1-(methylamino)carbonyl-propylaminocarbonyl-1H-carbazol-3-ylaminocarbonylbutylcarbamate (222a), a methyloxymethyl-4-pyridyl radical, in particular the compound 2,3,4,9-tetrahydro-3-(3-phenylpropyl)-O-(4-pyridinylmethyl)-1H-carbazole-3-methanol (287), 0059 a carboxyl radical, in particular the compound 2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazole-3-carboxylic acid (273), 0060 or a propenoic acid ethyl ester radical, in particular the compound ethyl 3-2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazol-3-yl-2-propenoate (289). 0061 Also especially preferred are compounds of general formula (I), in which radical R6 is: 0062 a carbonylvalylamide radical, in particular the compound phenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-(aminocarbonyl)-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino carbonyl-2-methylbutylcarbamate (58), 0063 a carbonylthreonylamide radical, in particular the compound phenylmethyl (1S,2S)-1-(3R)-3-(1S,2R)-1-(aminocarbonyl)-2-hydroxypropylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate, 0064 a cyclic carboxamide radical (such as, for example, a carbonylpropylamide radical, in particular the compound phenylmethyl (1S,2S)-1-(3R)-3-(2S)-2-(aminocarbonyl)-1-pyrrolidinylcarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamate (181a) 0065 or a carbonyloctahydroindolyl-2-carboxamide radical, in particular the compound phenylmethyl (1S,2S)-1-(3R)-3-(2S)-2-(aminocarbonyl)octahydro-1H-indol-1-ylcarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamate (190a)), 0066 a 4-carboxamidophenylcarboxamide radical, in particular the compound phenylmethyl (1S,2S)1-(3R)-3-4-(aminocarbonyl)phenylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate (62), 0067 a methylaminomethyl-2-pyridyl radical, in particular the compound 2,3,4,9-tetrahydro-3-(3-phenylpropyl)-N-(2-pyridinylmethyl)-1H-carbazole-3-methanamine (279), 0068 a carbonylvalinol radical, in particular the compounds phenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-(hydroxymethyl)-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate (267b) and 2,3,4,9-tetrahydro-N-(1S)-1-(hydroxymethyl)-2-methylpropyl-3-(3-phenylpropyl)-1H-carbazole-3-carboxamide (276) 0069 or a methylvalinol radical, in particular the compound (2S)-3-methyl-2-2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazol-3-ylmethylamino-1-butanol (284). 0070 Preferred, new tetrahydrocarbazole derivatives of general formula (I) according to the invention are also any compounds in which R7 is a hydrophobic radical that comprises alkyl, aryl and/or hetaryl structures. Especially preferred in this case are compounds of general formula (I), in which radical R7 is: 0071 a 2,3-biphenylpropionylamino radical, in particular the compound N-(3R)-2,3,4,9-tetrahydro-3-(1-oxo-2,3-diphenylpropyl)amino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamide (18), 0072 an indanoylamino radical, in particular the compound (3R)-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-3-(2,3-dihydro-1H-inden-1-yl)carbonylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide (162a), 0073 an indolylacetylamino radical, in particular the compound (3S)-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-3-(1H)-indol-3-ylacetyl)amino-1H-carbazole-3-carboxamide (164b), 0074 a 2-naphthylacetylamino radical, in particular the compound (3S)-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-3-(2-naphthalenylacetyl)amino-1H-carbazole-3-carboxamide (161b), 0075 or a 3-propionylamino radical, in particular the compound N-(3R)-2,3,4,9-tetrahydro-3-(2S,3S)-3-methyl-1-oxo-2-(1-oxo-3-phenylpropyl)aminopentyl-amino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamide (22). 0076 Also especially preferred are compounds of general formula (I), in which R7 is: 0077 a phenylmethylcarboxamide radical that is substituted in the aromatic system, in particular the compounds (3R)-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-3-(4-methylphenyl)acetylamino-1H-carbazole-3-carboxamide (165a), 0078 N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-3-(4-methoxyphenyl)-acetylamino-1H-carbazole-3-carboxamide (175), 0079 (3R)-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-3-(3-bromophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide (96), 0080 (3R)-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-3-(4-fluorophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide (91), 0081 (3R)-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-3-(4-chlorophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide (167a); 0082 a phenylhexylamine radical, in particular the compound (3R)-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-3-(6-phenylhexyl)amino-1H-carbazole-3-carboxamide (234a); 0083 or a phenylpropyl radical, in particular the compounds 6,8-dichloro-2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazole-3-carboxylic acid (275) and ethyl-6,8-dichloro-2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazole-3-carboxylate (272). 0084 Preferred are also any new compounds of general formula (I) according to the invention that are present in R-configuration in the carbon atom that is substituted by radicals R6 and R7, if radicals R6 and R7 together form an alpha-aminocarboxylic acid structural element. 0085 Most preferred for the purposes of this invention are the compounds phenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-(aminocarbonyl)-2-methylpropylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl carbamate (184a), phenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-(hydroxymethyl)-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate (267a), (2S)-1-(3R)-3-(4-chlorophenyl)acetylamino-2,3,4,9-tetrahydro-8-methoxy-1H-carbazol-3-ylcarbonyl-2-pyrrolidine carboxamide (189a) and 6,8-dichloro-2,3,4,9-tetrahydro-3-(3-phenylpropyl)-N-(2-pyridinylmethyl)-1H-carbazole-3-methanamine (283). 0086 Other representatives of new compounds of general formula (I) according to the invention including their production are indicated in the examples. 0087 The new tetrahydrocarbazole derivatives (I) according to the invention, as defined above, are ligands of GPCR and can be used in particular for inhibition, i.e., as antagonists of the gonadotropin-releasing hormone, for example for male birth control, for hormone therapy, for treatment of female subfertility or infertility, for female contraception and to combat tumors. 0088 In male birth control, the compounds according to the invention bring about a reduction in spermatogenesis. A combined administration with androgens, e.g., testosterone or testosterone derivatives, such as, for example, testosterone esters, preferably takes place. In this case, the administration of testosterone derivatives can be carried out by, for example, injection, e.g., by intramuscular depot injection. 0089 Compounds (1) according to the invention, optionally in combination with other hormones, e.g., estrogens and/or progestins, can also be used in hormone therapy, for example for treating endometriosis, uterus leiomyomas and uterine fibroids. Especially preferred are combinations of the GnRH antagonists according to the invention and tissue-selective partial estrogen agonists such as Raloxifene(R). In addition, the compounds according to the invention can be used in hormone replacement therapy. Moreover, compounds (1) according to the invention can be used for increasing female fertility, for example by inducing ovulation, and treating sterility. 0090 In contrast, new compounds (1) according to the invention are also suitable for contraception in females. Thus, the GnRH antagonist according to the invention can be administered on days 1 to 15 of the cycle together with estrogen, preferably with very low estrogen dosages. On days 16 to 21 of the intake cycle, progestagen is added to the estrogen-GnRH-antagonist combination. The GnRH antagonist according to the invention can be administered continuously over the entire cycle time. In this way, a reduction in the hormone dosages and thus a reduction in the side effects of unphysiological hormone levels can be achieved. In addition, advantageous effects in women who suffer from polycystic ovarian syndrome and androgen-dependent diseases, such as acne, seborrhea and hirsutism, can be achieved. An improved cycle monitoring relative to previous administration methods can also be expected. Further indications are benign prostate hyperplasia, gonad protection in chemotherapy, controlled ovarian stimulation/artificial reproduction techniques, infantile development disorders, e.g., Pubertas praecox and polycystic ovaries. 0091 Finally, compounds (I) according to the invention, as defined above, can also be used for the treatment of hormone-dependent tumor diseases, such as premenopausal breast cancer, prostate cancer, ovarian cancer and endometrial cancer, by the endogenous sex steroid hormones being suppressed. 0092 New compounds (1) according to the invention, as defined above, are suitable as GPCR ligands, in particular GnRH antagonists for treating the above-indicated pathologic conditions for administration to mammals, in particular to humans, but also for the purposes of veterinary medicine, e.g., in the case of domestic and working animals but also in the case of wild animals. 0093 The administration can be carried out in the known way, for example, orally or non-orally, in particular topically, rectally, intravaginally, nasally or by injections or implantation. Oral administration is preferred. New compounds (I) according to the invention are brought into a form that can be administered and are optionally mixed with pharmaceutically compatible vehicles or diluents. Suitable adjuvants and vehicles are described in, for example, Ullmann 's Encyclopedia of Technical Chemistry, Vol. 4, (1953), 1-39; Journal of Pharmaceutical Sciences, Vol. 52 (1963), 918 ff; issued by Czetsch-Lindenwald, Hilfsstoffe fr Pharmazie und angrenzende Gebiete Adjuvants for Pharmaceutics and Related Fields; Pharm. Ind. 2, 1961, 72 ff; Dr. H. P. Fiedler, Lexikon der Hilfsstoffe fr Pharmazie, Kosmetik und angrenzende Gebiete Dictionary of Adjuvants for Pharmaceutics, Cosmetics and Related Fields, Cantor, K. G., Aulendorf in Wrttemberg, 1971. 0094 Oral administration can be carried out, for example, in solid form as tablets, capsules, gel capsules, coated tablets, granulates or powders, but also in the form of a drinkable solution. For oral administration, the new compounds of general formula (I) according to the invention, as defined above, can be combined with known and commonly used physiologically compatible adjuvants and vehicles, such as, e.g., gum arabic, talc, starch, sugar, such as, e.g., mannitol, methyl cellulose, lactose, gelatin, surfactants, magnesium stearate, cyclodextrins, aqueous or non-aqueous vehicles, diluents, dispersing agents, emulsifiers, lubricants, preservatives and flavoring substances (e.g., ethereal oils). The compounds according to the invention can also be dispersed in a microparticulate, e.g., nanoparticulate composition. 0095 The non-oral administration can be carried out by, for example, intravenous, subcutaneous or intramuscular injection of sterile aqueous or oily solutions, suspensions or emulsions, by implants or by ointments, creams or suppositories. An administration as a timed-release form can optionally also be carried out. Implants can contain inert materials, e.g., biodegradable polymers or synthetic silicones, such as, e.g., silicone rubber. Intravaginal administration can be carried out by, e.g., vaginal rings. Intrauterine administration can be carried out by, e.g., diaphragms, etc. Moreover, a transdermal administration, in particular by a formulation suitable in this respect and/or suitable means such as, e.g., a patch, is also provided. 0096 As already mentioned above, new compounds (I) according to the invention can also be combined with other pharmaceutical active ingredients. Within the scope of a combination therapy, the individual active components can be administered simultaneously or separately, specifically either on the same path (e.g., orally) or on separate paths (e.g., orally and as an injection). They can be present or administered in a unit dose in the same or different amounts. A specific dosage regimen can also be used if this seems suitable. In this way, several of the new compounds (I) according to the invention can also be combined with one another. 0097 The dosage can vary within a wide range depending on the type of indication, the severity of the disease, the type of administration, the age, sex, body weight and sensitivity of the subject that is to be treated. This corresponds to the abilities of one skilled in the art to determine a pharmacologically effective amount of the combined pharmaceutical composition. Unit dosages of 1 g to 100 mg, especially preferably 1 g to 10 mg, and most preferably 1 g to 1 mg per kg of body weight of the subject that is to be treated are preferred. The administration can be carried out in an individual dose or several separate dosages. 0098 Accordingly, in another aspect of this invention, pharmaceutical compositions, as described above, that comprise at least one of new compounds (I) according to the invention, as defined above, as well as optionally pharmaceutically compatible vehicles and/or adjuvants, are also included by this invention. Preferred and especially preferred pharmaceutical compositions are any that comprise at least one of the above-mentioned preferred or especially preferred new compounds (I) according to the invention, in particular the above compounds that are mentioned by name. In pharmaceutical compositions according to this invention, in addition to at least one compound of general formula (I), as defined above, still other pharmaceutical active ingredients can also be present, as already presented above in more detail. 0099 In the pharmaceutical compositions according to the invention, at least one of new compounds (I) according to the invention, as defined above, is present in one of the above-mentioned preferred, especially preferred or most preferred unit doses, specifically preferably in a form of administration that makes oral administration possible. 0100 Moreover, in another aspect, this invention provides compounds of general formula (I), as defined above, for use as pharmaceutical agents. 0101 Tetrahydrocarbazole compounds of general formula (I) that are preferred according to the invention, as defined above, for use as pharmaceutical agents are in turn any compounds that were mentioned above as preferred and especially preferred compounds, in particular the preferred compounds according to the invention that are mentioned by name as well as the compounds that are mentioned in the examples. 0102 Relative to compounds (I) according to the invention that comprise pharmaceutical compositions as well as relative to compounds (I) according to the invention for use as pharmaceutical agents, reference is made to the remarks regarding the new compounds (I) according to the invention, as defined above, regarding possible uses and means of administration. 0103 In another aspect, this invention also provides the use of at least one tetrahydrocarbazole derivative of general formula (I) according to the invention, as defined above, wherebyas initially definedthe tetrahydrocarbazoles that are disclosed in the publications by Millet et al. and Maki et al. are excluded from the meaning of general formula (I), for the production of a pharmaceutical agent for treating GPCR-mediated diseases, especially for inhibiting the gonadotropin-releasing hormone (GnRH). 0104 Moreover, in another aspect, this invention provides the use of at least one compound of general formula (I) according to the invention, as defined above, but including the compounds excluded by name above, from the publications by Millet et al. and Maki et al., namely 3-amino-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, 3-amino-6-methoxy-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, 3-amino-6-benzyloxy-1,2,3,4-tetrahydro-carbazole-3-carboxylic acid, 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, methyl-3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate, ()-menthyl-3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate and 3-tert-butoxycarbonyl-amino-1,2,3,4-tetrahydrocabazole-3-carboxylic acid, for the production of a pharmaceutical agent for inhibiting the GnRH, preferably for male birth control, for hormone therapy, for treating female subfertility and infertility, for female contraception and to combat tumors. Stated more clearly, the designation a compound of general formula (I) as defined above, but including the compounds excluded by name above means a compound of general formula (I) 2

0105 in which: 0106 radical R1 is a hydrogen atom, a C2-C6 alkenyl radical or a C1-C6 alkyl radical and optionally can be substituted with an aryl radical, a hetaryl radical or the group COOR11, whereby the aryl radical or hetaryl radical can be substituted with up to three substituents, which are selected, independently of one another, from the group that consists of NO2, CH3, CF3, OCH3, OCF3 and halogen atoms, and 0107 radical R11 is a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 aralkyl radical, an aryl radical, a hetaryl radical or the group COCH3, and optionally can be substituted with a substituent that is selected from the group that consists of CONH2, COCH3, COOCH3, SO2CH3 and aryl radicals; 0108 radicals R2, R3, R4 and R5, independently of one another, in each case are a hydrogen atom, a halogen atom, the group COOH, CONH2, CF3, OCF3, NO2, CN, a C1-C6 alkyl radical, a C1-C6 alkenyl radical, a C1-C6 alkoxy radical, a C1-C12 aralkyl radical, an aryl radical or a hetaryl radical; 0109 radical R6 is the group CONR8R9, COOR8, CH2NR8R9, CH2R8, CH2OR8 or a C1-C12 alkenyl radical, which optionally is substituted with radicals R8 and R9, 0110 whereby radicals R8 and R9, independently of one another, in each case are a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 aralkyl radical, a C1-C12 hetaralkyl radical, an aryl radical or hetaryl radical, which can be substituted with one or more substituents, which are selected from the group that consists of OH, NH2, CONHR10, COOR10, NHC(NH)NH2 and halogen atoms, 0111 whereby radical R10 is a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 aralkyl radical, an aryl or hetaryl radical and optionally is substituted with the group CON(R11)2, 0112 or whereby radicals R8 and R9 together can form a ring structure that either exclusively consists of carbon atoms or, mixed, consists of carbon and heteroatoms; 0113 radical R7 is a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 alkenyl radical, a C1-C12 aralkyl radical, an aryl radical or hetaryl radical, the group NR2R13, NHCOR14, NHCONHR4, NHCOOR4 or NHSO2R4, and optionally can be substituted with one or more substituents that are selected from the group that consists of OH, NH2, CONH2, COOH and halogen atoms, 0114 radicals R12 and R13, independently of one another, in each case are a hydrogen atom, a C2-C6 alkenyl radical or a C1-C12 alkyl radical, and optionally can be substituted with one or more aryl radicals or hetaryl radicals, which can be substituted in turn with up to three substituents, which are selected, independently of one another, from the group that consists of NO2, CH3, CF3, OCH3, OCF3 and halogen atoms, 0115 and radical R14 is a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 alkenyl radical, a C1-C12 aralkyl radical, an aryl radical or a hetaryl radical, which optionally can be substituted with one or more substituents, which are selected from the group that consists of NO2, CH3, OR11, CF3, OCF3, OH, N(R11)2, OCOR11, COOH, CONH2, NHCONHR11, NHCOOR11, and halogen atoms; 0116 and radicals Ra, Rb, Rc, Rd, Re and Rf, independently of one another, in each case are a hydrogen atom, a halogen atom, the group COOH, CONH2, CF3, OCF3, NO2, CN, a C1-C6 alkyl radical, C1-C6 alkoxy radical, an aryl radical or a hetaryl radical. 0117 The indications already mentioned in connection with the new compounds of general formula (I) according to the invention, as defined above (i.e., excluding the compounds mentioned by name above and disclosed in the publications by Maki et al. and Millet et al.) were already provided above in reference to the new compounds (I) according to the invention. The preferred and especially preferred compounds in the use of the above-defined compounds for the production of a pharmaceutical agent for inhibiting the GnRH are identical to the preferred and especially preferred compounds already mentioned above in connection with the new compounds of general formula (I) according to the invention, as defined above. 0118 In another aspect, this invention provides the use of a compound (I) according to the invention as defined above, but also including compounds initially excluded by name for male birth control or for female contraception. Preferred and especially preferred compounds according to the invention for this use are any compounds that were already initially mentioned as preferred or especially preferred compounds of general formula (I) according to the invention, as defined above. 0119 Moreover, this invention provides a process for male birth control or for female contraception that comprises the administration of an amount of a compound according to the invention that is effective for male birth control or for female contraception as defined in the paragraph directly above, to a subject, preferably a mammal, especially preferably a human. 0120 In another aspect, this invention relates to a process for treating GPCR-mediated pathologic conditions. The process comprises the administration of at least one compound (I) according to the invention, as defined above, to a mammal, especially a human, in whom such a treatment is necessary. The administration is usually carried out in a pharmaceutically effective amount. As already explained above in reference to the new compounds (I) according to the invention as well as the pharmaceutical compositions according to the invention, one skilled in the art must rely on his technical knowledge to determine a pharmaceutically effective amount based on the special requirements of the individual case. Compounds (I) according to the invention, however, are preferably administered in a unit dose of 1 g to 100 mg, especially preferably 1 g to 10 mg and most preferably 1 g to 1 mg per body weight to the subject under treatment. The preferred form of administration is oral administration. It is also provided to administer one or more of compounds (I) according to the invention in combination with at least one other active ingredient, as already explained above. 0121 Moreover, this invention also relates to a process for inhibiting GnRH in a patient, comprising the administration of a pharmaceutically effective amount of a compound of general formula (I), as defined above, but including the compounds excluded by name above to a patient who requires such a treatment. The process is preferably used in male birth control, hormone therapy, female contraception, treatment of female subfertility or infertility and to combat tumors. 0122 Finally, in a last aspect, this invention also provides a process for the production of new tetrahydrocarbazole derivatives of general formula (I) according to the invention. The process for the production of the compounds of general formula (I) according to the invention can be performed in a different way, thus, e.g., in liquid phase or as partial or complete solid-phase synthesis. The selection of suitable synthesis conditions for the production of individual representatives of the compounds of general formula (I) can be made by one skilled in the art based on his general technical knowledge. Below, a process for the production of compounds of general formula (I) according to the invention is first described in general terms. Then, a specific variant of the process, namely a solid-phase process, is described. For further illustration of this invention, numerous representatives of the compounds of general formula (I) are found in the listed examples. 0123 A process for the production of the compounds of general formula (I) according to the invention is preferably performed as follows: 0124 The central tetrahydrocarbazole skeleton is accessible by a Fischer-indole synthesis that is known in the art. To this end, a suitably substituted cyclohexanone derivative that is optionally provided with protective groups is condensed with the phenylhydrazine derivative that is desired in each case, also suitably substituted and optionally provided with protective groups (e.g., according to Britten & Lockwood, J. C. S. Perkin I 1974, 1824 or according to Maki et al., Chem. Pharm. Bull. 1973, 21, 240). In particular, the cyclohexanone skeleton is substituted in positions 3,3, 5,5 and 6,6 by radicals Ra to Rf as well as in positions 4,4 by the radicals or optionally by precursors of radicals R6 and R7. The phenylhydrazine skeleton is optionally substituted by radicals R2 to R5. Phenylhydrazine derivatives that are not commercially available can be produced by the process that is known to one skilled in the art. Position isomers that are optionally produced upon the condensation of the cyclohexanone derivative and the phenylhydrazine derivative can be separated by chromatographic methods, such as, e.g., HPLC. 0125 After the synthesis of the central tetrahydrocarbazole skeleton, radical R1 can be introduced by N-alkylation of the nitrogen atom in 9-position with corresponding R1-halides with use of a base (e.g., according to Pecca & Albonico, J. Med. Chem. 1977, 20, 487 or also according to Mooradian et al., J. Med. Chem. 1970, 13, 327). 0126 Radicals R6 and R7, as was already indicated above, are introduced in a different way depending on their type, which is explained in more detail below. 0127 In these radicals, -aminocarboxylic acid structures are accessible by treatment of ketones with NH4(CO)3 and KCN under Schotten-Baumann conditions that are known in the art and subsequent alkaline hydrolysis of the formed hydantoin (Britten & Lockwood, J. C. S. Perkin I 1974, 1824). 0128 Amide radicals are preferably produced with the process from peptide chemistry that is known in the art. To this end, the acid component is activated with an activating reagent such as DCC or else HATU (Tetrahedron Lett. 1994, 35, 2279) and is condensed in the presence of a base such as DIPEA and/or DMAP with the amino component. 0129 Ester radicals can be obtained according to analogous conditions with use of the desired alcohols. The solvent that is used in this case is preferably anhydrous. 0130 Secondary or tertiary amine radicals are obtained from primary amines either by nucleophilic substitution of alkyl halides or by reductive amination of aldehydes/ketones (e.g., J. Org. Chem. 1996, 61, 3849 or Synth. Comm. 1994, 609). 0131 Sulfonamide radicals are obtained from the corresponding amines by reaction with sulfonic acid chlorides. 0132 Urea radicals are obtained if the amines are reacted with corresponding isocyanates. 0133 Urethane radicals can be produced by corresponding alcohols being preactivated with carbonyldihydroxy benzotriazole ((HOBt)2CO) and then reacted with amines (Warass et al., LIPS 1998, 5, 125). 0134 Alcohols are accessible from carboxylic acid esters by reduction with LiAlH4. 0135 Aldehyde radicals are obtained from alcohol precursors by being oxidized with DMSO/oxalyl chloride, for example, under Swem conditions that are known in the art (Pansavath et al., Synthesis 1998, 436). 0136 Substituted amine radicals are obtained by reductive amination of amines with aldehydes (J. Org. Chem. 1996, 61, 3849). 0137 Ether radicals can be obtained by the alcohol precursors with a base such as NaH being deprotonated under Williams conditions that are known in the art and then reacted with an alkyl halide. 0138 Double bonds in the radicals can be introduced by an aldehyde or ketone precursor being reacted according to Wittig conditions that are known in the art with corresponding phosphonylides. 0139 A solid-phase process for the production of the compounds of formula (I) according to the invention preferably comprises steps (a) to (d) that are explained in more detail below: 0140 Step (a) essentially proceeds analogously to a Fischer-indole synthesis, e.g., according to Britten & Lockwood, J C. S. Perkin I 1974, 1824; Maki et al., Chem. Pharm. Bull. 1973, 21, 240 or Hutchins & Chapman, Tetrahedron Lett. 1996, 37, 4869 and comprises the condensation of a cyclohexanone derivative (II) that contains group G and that is anchored to a solid phase SP via a linker L that is suitable for forming radical R6

0141 whereby in the event that radical R7 is a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 aralkyl radical or a hetaryl radical, group G is equal to radical R7, and in the event that radical R7 has a different meaning than is indicated in formula (I) for R7, group G is equal to a group NH-Pg, whereby Pg stands for a protective group with a phenylhydrazine derivative (III) that is substituted by R2 to R5

0142 in the presence of an acid, preferably acetic acid, and a metal salt; preferably ZnCl2. As a solvent, DMF is preferred. Radicals Ra to Rf are defined as indicated above in formula (I). Certain substituents or groups can optionally also be present in protected form, whereby the protective groups are removed at a suitable time in the course of the process again according to a process that is known in the art. 0143 For the purpose of this invention, especially Rink amide resins (Rink, Tetrahedron Lett. 1989, 28, 3787), HMB resins (Sheppard et al., Int. J. Peptide Protein Res. 1982, 20, 451), Wang resins (Lu et al., J. Org. Chem. 1981, 46, 3433) or chlorotrityl resins (Barlos et al., Int. J. Peptide Protein Res. 1991, 38, 562) are suitable as solid phase SP, if the cyclohexanone derivative (II) is to be anchored by means of an (amino-)carboxylic acid to solid phase SP. To anchor the alcohol precursors of the cyclohexanone derivative (II), the DHP linker (Liu & Elman, J. Org. Chem. 1995, 60, 7712) can be used. Aromatic compound precursors of the cyclohexanone derivative (II) can be anchored in a traceless manner to triazine resins (Brse et al., Angew. Chem. Int. Ed. 1998, 37, 3413). 0144 Protective group Pg that is optionally included in group G and that protects an -amino group NH2 is preferably an Fmoc (9-fluorenylmethoxycarbonyl) protective group, but can also be another commonly used amino protective group, e.g., from the series of alkoxycarbonyl protective groups (such as, e.g., the Z (benzyloxycarbonyl) group or the Boc (tert-butoxycarbonyl) group) or another suitable protective group, e.g., a trityl (triphenylmethyl) protective group. 0145 Linker L is constituted in such a way that after corresponding derivatization (steps (b) and (c)) and working-up (step (d)) in the end product, the desired radical R with one of the meanings that is indicated above for R6 results in the tetrahydrocarbazole derivative of general formula (I). To illustrate the composition of linker L, the latter can then be explained by way of example in the event that R6 is equal to group CONR8R9. 0146 In the event that in the product of formula (I) according to the invention radical R6 has the meaning CONR8R9, a compound Pg-N(R8)R9COOH that forms linker L is first anchored by means of an activating reagent, such as DCC (dicyclohexyl-carbodiimide) or HATU (0-(7-azabenzotriazol-1-yl)-N,NN,N-tetramethyluronium hexafluorophosphate) to solid phase SP via free amino groups of SP, whereby Pg and SP have the meaning indicated above and R9 forms a portion of subsequent radical R9. Protective group Pg is then cleaved off, e.g., in the case of an Fmoc protective group by means of piperidine/DMF. From this results a compound HR8NR9CONHSP. The latter compound is now reacted with a precursor of cyclohexanone derivative (II), namely the cyclohexanone-carboxylic acid (II) 5

0147 in turn with use of an activating reagent such as DCC or HATU, from which finally the cyclohexanone derivative (II), as defined above, results. Linker L has the meaning CONR8R9CONH-SP for the above-described case. Isomers of any type (enantiomers, diastereomers or position isomers) that are optionally produced can be separatedas well as at other sites of the described production processin a known-way by means of HPLC. 0148 Then, actual step (a), i.e., the condensation of cyclohexanone derivative (II), is carried out with substituted phenylhydrazine derivative (III) and optionally cleavage of protective group Pg in group G by means of, e.g., piperidine (in the case of an Fmoc protective group), so that a free -amino group is produced again at this point. 0149 In the event that radical R7 is the group NHCOR14, NHSO2R14, NR12R13 (whereby R12 and R13 are not simultaneously hydrogen atoms), NHCONHR14 or NCOOR14, a derivatization of the now unprotected -amino group of resin-bonded cyclohexanone derivative (II) finally takes place in step (b), such that the various alternative radicals R7, defined above, can be formed. 0150 Depending on the type of desired radical R7 in the tetrahydrocarbazole end product (I) according to the invention, in this case the procedure is as follows: 0151 In the event that R7 is the group NHCOR14, the reaction product from step (a) is reacted with a carboxylic acid R14COOH in the presence of an activating reagent, such as, e.g., DCC or HATU, and in the presence of a base, such as, e.g., DIPEA (diisopropylethylamine) or DMAP (4-dimethylaminopyridine) according to known processes for forming peptide bonds (cf., e.g., Tetrahedron Lett. 1994, 35, 2279; Alternative (i)). 0152 In the event that R7 is a sulfonamide group NHSO2R14, the reaction product from step (a) is reacted with a sulfonic acid derivative R14SO2X, whereby X is a leaving group, preferably a halogen atom, especially a chlorine atom, in the presence of a base, such as, e.g., DMAP or DIPEA (cf., e.g., Gennari et al., EJOC 1998, 2437; Alternative (ii)). 0153 In the event that R7 is the group NR 12R3 (whereby R12 and R13 are not simultaneously hydrogen atoms), and in the event that radical R12 is a hydrogen atom, the reaction product from step (a) is reacted with a reagent R13X, whereby X is a leaving group, such as, e.g., a halide atom, especially a chloride atom, in the presence of a base, such as, e.g., DBU or DIPEA (cf. Green, JOC 1995, 60, 4287 or JOC 1996, 61, 3849) or with an aldehyde R13CHO in the presence of a reducing agent, such as, e.g., NaH/B(OAc)3. In the event that none of radicals R12 and R13 are a hydrogen atom, the reaction product from step (a) is reacted with a ketone R12COR13 in the presence of a reducing agent (cf. Ellmann et al., JOC 1997, 62, 1240 or Synth. Commun. 1994, 609; Alternative (iii)). In the event that in R7 equal to NR12R13, both radicals R12 and R13 are hydrogen atoms, alternative (vi) below applies. 0154 In the event that R7 is the group NHCONHR14 (a urea derivative), the reaction product from step (a) is reacted with an isocyanate R14NCO (cf. Brown et al., JACS 1997, 119, 3288; Alternative (iv)). 0155 In the event that R7 is a carbamate or urethane group NHCOOR14, the reaction product from step (a) is reacted by alcohol HOR14 that is preactivated by carbonyldihydroxybenzotriazole ((HOBt)2CO) (cf. Warass et al., LIPS 1998, 5, 125; Alternative (v)). 0156 In the event that R7 is a hydrogen atom, a C1-C12 alkyl radical, a C1-C12 aralkyl radical, an aryl radical, a hetaryl radical or the group NH2 (i.e., in R7 equal to NR12R13, both radicals R12 and R13 are hydrogen atoms), step (b) is eliminated, since no further derivatization is necessary (alternative (vi)). 0157 Analogously to step (b) that is explained above, step (c), i.e., the derivatization on the indole-nitrogen atom, also corresponds to various alternatives that are explained in more detail below: 0158 For cases (i) to (v) that are defined above in step (b), a deprotonation of the reaction product that is obtained in (b) takes place by means of a base, such as, e.g., NaH or NaHMD, and a subsequent derivatization by means of a group R1X, whereby X is a leaving group, e.g., a halide atom, in particular a chloride atom (cf. Collini & Ellingboe, Tetrahedron Lett. 1997, 38, 7963; Pecca & Albonico, J. Med. Chem. 1977, 20, 487 or Mooradian et al., J. Med. Chem. 1970, 13, 327). 0159 For case (vi) that is defined above in step (b), i.e., if step (b) is omitted, a deprotonation of the reaction that is obtained in (a) takes places analogously to the descriptions above by means of a base, such as, e.g., NaH or NaHMDS and a subsequent derivatization by means of a group R1X, whereby X is a leaving group, e.g., a halide atom, in particular a chloride atom. 0160 Finally, step (d) essentially comprises the cleavage of the reaction product that is obtained in (c) from solid phase SP. In the case of Wang, trityl, DHP and Rink amide resin, the cleavage of the reaction product that is obtained in (c) takes place with the aid of an acid, especially with TFA (trifluoroacetic acid). In the case of an aminolytic cleavage of an HMB resin, for example, ammonia in methanol is used as a cleavage reagent. Then, the desired product is isolated in the usual way. 0161 Embodiments for the production of tetrahydrocarbazole derivatives according to the invention are cited below. 0162 Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. 0163 In the foregoing and in the following examples, all temperatures are set forth uncorrected in degrees Celsius and, all parts and percentages are by weight, unless otherwise indicated.

EXAMPLES 0164 I. General Synthesis Instructions for Compounds According to the Invention 0165 A. Coupling of Carboxylic Acids to the Rink Amide Resin: 0166 0.1 mmol of Fmoc-protected Rink amide resin (166 mg, concentration 0.6 mmol/g) is presteeped in a vessel with a fritted bottom with 1.5 ml of DMF for 20 minutes. After being suctioned off, 1.5 ml of 20% piperidine/DMF is added, and it is stirred for 5 minutes. After being suctioned off, 1.5 ml of 20% piperidine/DMF is added again and stirred for 15 minutes. After being suctioned off, it is washed four times with DMF. Then, 675 l of a 0.267 M solution of Fmoc-protected amino-carboxylic acid in DMF, 675 l of HATU solution (0.267 M in DMF) and 150 l of NMM solution (2.4 M in DMF) as well as 0.01 mmol of DMAP are added and stirred for 4 hours at 40 C. After being suctioned off, the same reagents are added again and stirred for 4 hours at 40 C. Then, it is suctioned off and washed four times with DMF. 0167 B. Coupling of Carboxylic Acids to the Trityl Resin: 0168 2.98 mmol of Fmoc-protected amino-carboxylic acid is dissolved in 30 ml of dry dichloromethane, mixed with 14.3 mmol (2.45 ml) of DIPEA and added to 2.98 mmol of 2-chlorotrityl chloride resin (2 g, concentration 1.49 mmol/g of resin). After two hours of shaking, the resin is suctioned off via a frit and washed three times with 20 ml of dichloromethane/MeOH/DIPEA 17:2:1. Then, it is washed three times with 20 ml of dichloromethane, three times with methanol and three times with 20 ml of ether and dried in a vacuum. A resin with a concentration of 0.5 to 1 mmol of amino-carboxylic acid per g of resin is obtained. 0169 C. Coupling of Carboxylic Acids to the HMB Resin: 0170 21.3 mmol of amino-carboxylic acid and 21.3 mmol of HATU are dissolved in 60 ml of DMF and mixed with 63.9 mmol (10.9 ml) of DIPEA. After 5 minutes, 5 g of polystyrene-HMB resin (concentration 0.71 mmol/g of resin) is added and shaken for 5 minutes at room temperature. Then, 21.3 mmol (2.6 g) of DMAP is added and shaken for 1 hour at room temperature. Then, the resin is suctioned off and washed once each with 100 ml of DMF, DCM and DMF. The resin is mixed with 100 ml of 10% Ac2O (acetic anhydride)/DMF/5% DMAP and shaken for 15 minutes. After being suctioned off, it is washed three times each with 100 ml of DCM and ether and dried in a vacuum. 0171 D. Coupling of Carboxylic Acids to the Wang Resin: 0172 54.6 mmol of carboxylic acid and 27.3 mmol (4.2 ml) of DIC are dissolved in 500 ml of dry DCM and stirred for 10 minutes at room temperature. After the precipitated urea is filtered out, the solution is evaporated to the dry state, and the residue is dissolved in 160 ml of dry DMF. The solution is added to 4.55 mmol (5 g, concentration 0.91 mmol/g of resin) of Wang resin that is presteeped in DMF and mixed with 4.55 mmol (556 mg) of DMAP. After 1.5 hours of shaking at room temperature, the resin is suctioned off and taken up in 100 ml of 10% Ac2O/DMF/5% DMAP and shaken for 15 minutes. After being suctioned off, it is washed three times each with 100 ml of DCM and ether and dried in a vacuum. 0173 E. Coupling of an Alcohol to the DHP Resin: 0174 0.5 mmol of DHP resin (0.5 g, concentration density of 1 mmol/g) is presteeped for 15 minutes in 2 ml of dichloroethane. 2 ml of a solution of 0.75 M alcohol/0.37 M pyridinium paratoluenesulfonate is added thereto and stirred for 16 hours at 80 C. After cooling to room temperature, 5 ml of pyridine is added, shaken briefly and suctioned off. It is washed twice each with 5 ml of DMF, DCM and hexane. 0175 F. Protection Removal of a Resin-Bonded Fmoc Protective Group: 0176 1.5 ml of 20% piperidine/DMF is added to 0.1 mmol of a resin-bonded Fmoc group and stirred for 5 minutes. After being suctioned off, 1.5 ml of 20% piperidine/DMF is added again, and it is stirred for 15 minutes. After suctioning off, it is washed four times with DMF. 0177 G. Coupling of a Carboxylic Acid to Resin-Bonded Amino Functions: 0178 675 l of a 0.267 M solution of Fmoc-protected amino-carboxylic acid in DMF, 675 l of HATU solution (0.267 M in DMF) and 150 l of NMM solution (2.4 M in DMF) as well as 0.01 mmol of DMAP are added to 0.1 mmol of resin-bonded amino functions and stirred for 4 hours at 40 C. After being suctioned off, the same reagents are added again and stirred for 4 hours at 40 C. Then, it is suctioned off and washed four times with DMF. 0179 H. Coupling of Acetic Acid to Resin-Bonded Amino Functions: 0180 1.5 ml of a solution of 10% acetic anhydride in DMF is added to 0.1 mmol of resin-bonded amino functions and stirred for 15 minutes at room temperature. Then, it is suctioned off and washed four times with DMF. 0181 I. Synthesis of Tetrahydrocarbazoles Starting from Resin-Bonded Cyclohexanones: 0182 Before the reaction, 0.1 mmol of cyclohexanone resin is washed twice with 2 ml of DMF and twice with 2 ml of acetic acid. Then, 1 ml of DMF and 2 ml of 0.5 M hydrazine/0.5 M of ZnCl2 in acetic acid are added to the resin and stirred for 20 hours at 70 C. Then, it is suctioned off and washed twice with 2 ml of acetic acid and 2 ml of DMF. 0183 J. Synthesis of Sulfonamides Starting from Resin-Bonded Amides: 0184 The resin is washed twice with 2 ml each of DMF and DCE. 1 ml of 0.5 M sulfonic acid chloride in DCE as well as 400 l of 2.5 M NMM/1 equivalent of 0.25 M DMAP in DMF are added to 0.1 mmol of resin-bonded amine. After 12 hours of stirring at 60 C., it is suctioned off, and the coupling is repeated. After being suctioned off, it is washed four times with 2000 ml of DMF. 0185 K. Synthesis of Ureas by Reaction of Resin-Bonded Amine with Isocyanates: 0186 2 ml of 0.5 M isocyanate in DCM is added to 0.11 mmol of resin-bonded amine and stirred for 18 hours at room temperature. After being suctioned off, it is washed four more times with DMF. 0187 L. Synthesis of Carbamates by Reaction of Resin-Bonded Amine with Preactivated Alcohols: 0188 For preactivation, 0.4 M alcohol and 0.39 M dibenzotriazolyl carbonate and 0.39 M pyridine in DMF are stirred at 40 C. for 15 minutes. 1 mmol of resin-bonded amine is mixed with 1 ml of preactivated alcohol, and 167 ml of 2.4 M NMM in DMF is added. After 4 hours of stirring at 60 C., it is suctioned off and washed four times with DMF. 0189 M. Synthesis of N-Alkylamines by N-Alkylation of Resin-Bonded Amines with Alkyl Halides and Catalytic KI: 0190 1 ml of 0.5 M halide/0.05 M KI in DMF and 416 l of 2.4 M DIPEA in DMF are added to 0.1 mmol of resin-bonded amine and stirred for 12 hours at 90 C. After being suctioned off, the resin is washed four times with 2 ml of DMF. 0191 N. N-Alklylation of Resin-Bonded Indole Nitrogens with Halide/NaH in DMF: 0192 1 ml of DMF and 0.5 mmol of NAH (55% suspension in oil) is added to 0.1 mmol of resin-bonded amine. After 30 minutes of stirring at room temperature, 1 ml of 0.5 M halide in DMF is added and stirred for 8 hours at 45 C. Then, it is suctioned off and washed twice each with 2 ml of methanol, DMF, methanol and DMF. 0193 O. Cleavage of Wang, Trityl, DHP, and Rink Amide Resins: 0194 2 ml of a 95% TFA/5% H2O solution is added to 0.1 mmol of resin and shaken for 3 hours at room temperature. Then, the resin is filtered off and rewashed with another 2 ml of TFA. The combined TFA solutions are evaporated to the dry state and yield the crude products. 0195 P. Aminolytic Cleavage of HMB Resin: 0196 2 ml of DMF and 2 ml of 7 M NH3 in methanol are added to 0.1 mmol of resin and shaken for 18 hours at room temperature. Then, the resin is filtered off and rewashed with DMF. The combined solutions are evaporated to the dry state and yield the crude product. 0197 Production of Required Starting Compounds: 0198 3-(9H-Fluoren-9-ylmethoxy)carbonylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic Acid I 0199 38.4 mmol (6.0 g) of 4,4-ethylenedioxycyclohexanone and 39.8 mmol (4.3 g) of phenylhydrazine are dissolved separately in 50 ml or 10 ml of water and then mixed. After 10 minutes of stirring, the resulting milky emulsion is extracted five times with ethyl acetate, dried with MgSO4 and evaporated to the dry state. Yield: 9.2 g of orange oil. 0200 9.2 g of unpurified phenylhydrazone is dissolved at room temperature in 240 ml of toluene and mixed with 4.9 g of ZnCl2 that is freshly ground in a mortar. After 90 minutes of reflux in a water separator, most of the toluene is distilled off, mixed with an excess of 2N NaOH and extracted three times with ethyl acetate. The extract is washed with brine, dried with MgSO4, and the solvent is distilled off. The remaining black oil is purified on silica gel with ethyl acetate/hexane 1:9. Yield: 2.7 g of beige solid. 0201 11.6 mmol (2.7 g) of 1,2,4,9-tetrahydrospiro3H-carbazole-3,2*-1,3doxolane and 640 mg of p-toluenesulfonic acid are taken up in 70 ml of acetone and stirred for 2.5 hours at room temperature. The solution is added to NaHCO3 solution, extracted with ethyl acetate, washed with brine, dried with MgSO4 and concentrated by evaporation. 2.13 g of reddish-brown solid remains. After recrystallization from ether, 1.1 g of beige-colored solid is obtained. 0202 60.2 mmol (11.1 g) of 1,2,4,9-tetrahydrospiro-3H-carbazcl3-one, 8.3 g of KCN, and 22.0 g of (NH4)2CO3 are heated at 80 C. in 550 ml of 60% ethanol for 3 hours in an autoclave. After cooling to room temperature, the reaction mixture is added to ice water, and the precipitated solid is filtered off. Yield: 10.1 g of gray solid. 0203 44.2 mmol (11.3 g) of 1,2,4,9-tetrahydrospiro3H-carbazole-3,4-imidazolidine-2,5-dione is heated to 150 C. with 62 g of Ba(OH)28H2O in 145 ml of H2O for 13 hours. After cooling to room temperature, the viscous mass is mixed with 37 g of (NH4)2CO3 while being stirred and heated for 30 minutes to 100 C. After cooling to room temperature, it is filtered off, rewashed with water, and the filtrate is evaporated to the dry state. Yield: 7.7 g of beige solid. 0204 26 mmol (5.8 g) of 3-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid in 26 ml of 1N NaOH and 26 mmol (8.76 g) of Fmoc-ONSu in 28 ml of acetonitrile are combined at room temperature and diluted with 130 ml of acetonitrile/H2O 1:1. After two hours, the pH is readjusted to 9 (1.5 ml) with NEt3 and stirred overnight at room temperature. Then, another 6.3 g (18.7 mmol) of Fmoc-ONSu, dissolved in 19 ml of acetonitrile, is added and stirred for another two hours while the pH is monitored. After distillative removal of the acetonitrile, it is acidified with 0.01 M HCl and extracted with ethyl acetate. The extract is washed neutral, dried with Na2SO4 and spun in until a dry state is reached. Recrystallization is carried out from ether/hexane. Yield: 10.7 g. 0205 1H-NMR (d6-DMSO): 2.07 ppm (m, 1H); 2.50 (m, 1H); 2.70 (bs; 2H); 3.04 (q, 2H); 4.17 (m, 2H); 4.28 (m, 2H); 6.92 (tr, 2H); 6.99 (tr, 2H); 7.23 (tr, 2H); 7.24-7.35 (m, 3H); 7.38 (tr, 2H); 7.62 (s, 1H); 7.68 (dd, 2H); 7.87 (d, 2H); 10.71 (s, 1H). 0206 Melting point: 119 C. 0207 The separation into the two enantiomers is carried out by chiral HPLC. 0208 (R)-3-(9H-Fluoren-2-ylmethoxy)carbonyl/amino-2,3,4,9-tetrahydro-H-carbazole-3-carboxylic Acid 1a 0209 tR6.4 minutes (Chiralcel OD 10 m LC50 2504.6 cm, hexane/isopropanol 75:25, 80 ml/minute) 0210 (S)-3-(9H-Fluoren-9-ylmethoxy)carbonyl/amino-2,3,4,9-tetrahydro-H-carbazole-3-carboxylic Acid 1b 0211 tR7.5 minutes (Chiralcel OD 10 m of LC50 2504.6 cm, hexane/isopropanol 75:25, 80 ml/minute) 0212 1-(9H-Fuoren-9-ylmethoxy)carbonylamino-4-oxocyclohexanecarboxylic Acid 2 0213 320 mmol (50 g) of 4,4-ethylenedioxycyclohexanone is suspended in 800 ml of 50% EtOH and mixed with 1500 mmol (144.5 g) of (NH4)2CO3 and 640 mmol (41.7 g) of KCN. After 5 hours of stirring at 60 C., the ethanol is removed in a vacuum, and the aqueous residue is filtered off with ice after cooling, rewashed with water and dried. Yield: 72.4 g of 4,4-1,4-dioxa-9,11-diazadispiro4.2.4.2tetradecane-10,12-dione. 0214 295 mmol (66.8 g) of 4,4-1,4-dioxa-9,11-diazadispiro4.2.4.2tetradecane-10,12-dione and 826 mmol (260.6 g) of Ba(OH)28H2O are stirred in 2.5 l in an autoclave for 6 hours at 150 C. After cooling to room temperature, 1032 mmol (99.2 g of (NH4)2CO3 is added to the solution and stirred for one hour at 60 C. The suspension is filtered, rewashed, and the filtrate is freeze-dried. The residue is recrystallized from H2O/MeOH. Yield: 45.4 g of 8-amino-1,4-dioxaspiro4,5decane-8-carboxylic acid. 0215 213 mmol (42.9 g) of 8-amino-1,4-dioxaspiro4,5decane-8-carboxylic acid in 213 ml of 1N NaOH and 213 mmol (71.9 g) of Fmoc-ONSu in 240 ml of acetonitrile are combined and diluted with 1000 ml of acetonitrile/H2O 1:1. After the pH is set at 9, it is stirred overnight at room temperature. After the acetontrile is removed in a rotary evaporator, it is acidified with 0.01 M HCl and extracted with ethyl acetate. The extract is washed neutral, dried with Na2SO4 and evaporated to the dry state. The residue is recrystallized from ethyl acetate/hexane. Yield: 79.0 g of 8-(9H-fluoren-9-ylmethoxy)carbonylamino-1,4-dioxaspiro4,5decane-8-carboxylic acid. 0216 187 mmol (79 g) of 8-(9H-fluoren-9-ylmethoxy)carbonylamino-1,4-dioxaspiro4,5decane-8-carboxylic acid is taken up in 3.51 of acetone/0.1 M HCl 1:1 and stirred for 4 hours at room temperature. The acetone is drawn off in a rotary evaporator, and the precipitated product is filtered off, rewashed with water and dried. Yield: 68.7 g of 2. 0217 1H-NMR (d6-DMSO): 1.52-1.73 (m, 4H); 1.82-2.14 (m, 4H); 4.27 (m, 3H); 7.85 (tr, 2H); 7.42 (tr, 2H); 7.67 (s, 1H); 7.75 (d, 2H); 7.91 (d; 2H) 0218 Melting point: 157 C. 0219 4-Oxocyclohexanecarboxylic Acid 3 0220 20 mmol (3.4 g) of 4-oxocyclohexanecarboxylic acid ethyl ester is suspended in 40 ml of 2% H2SO4 and stirred for 2 hours at 90 C. Then, it is extracted 4 times with ethyl acetate, dried with Na2SO4, and solvent is removed. Recrystallization is carried out from ether/hexane and yields 2.9 g of white solid 3. 0221 1H-NMR (d6-DMSO): 1.72 (m, 2H); 2.08-2.18 (m, 2H); 2.19-2.47 (m, 4H); 2.72 (m: 1H); 12.23 (bs; 1H) 0222 4-Chloro-3-(phenylamino)carbonylaminobenzeneacetic Acid 4 0223 18.55 mmol (2.21 g) of SOCl2 is added slowly while being cooled with ice and while being stirred to 18.55 mmol (4 g) of 4-chloro-3-nitrobenzeneacetic acid in 50 ml of MeOH. After 30 minutes of stirring, it is allowed to heat to room temperature, and another 3.71 mmol (0.44 g) of SOCl2 is added. After being stirred overnight, it is refluxed for 30 minutes. After the solvent is drawn off, it is recrystallized from ether/hexane. Yield: 3.43 g of methyl 4-chloro-3-nitrobenzeneacetate as a yellowish solid. 0224 13.07 mmol (3.0 g) of methyl 4-chloro-3-nitrobenzeneacetate and 198.8 mmol (13.0 g) of Zn dust are refluxed in 500 ml of MeOH for 10 minutes. Then, 13 ml of concentrated HCl is added in drops under reflux and refluxed for another 30 minutes. The suspension is hot-filtered, the methanol is distilled off, and the residue is set at pH 14 with NaHCO3 solution. Extraction with ethyl acetate, drying with Na2SO4 and distillation of the solution yields 2.3 g of methyl 3-amino-4-chlorobenzeneacetate as a beige solid. 0225 2.08 mmol (415 mg) of methyl 3-amino-3-chlorobenzeneacetate is dissolved in 40 ml of DCM, and mixed at 0 C. with 0.83 mmol (246.3 mg) of triphosgene and 0.6 ml of pyridine. After one hour of stirring at 0 C., 10.4 mmol (1.11 g) of benzylamine is added, and stirring is continued overnight at room temperature. It is extracted with DCM/H2O, the organic phase is dried, and solvent is removed. Yield: 727 mg of methyl 4-chloro-3-(phenylamino)carbonylaminobezeneacetate. 0226 2.98 mmol (990 mg) of methyl 4-chloro-3-(phenylamino)carbonyl-aminobenzeneacetate is taken up in 10 ml of methanol and mixed with 6 mmol of 1N NaOH. After 2 hours of stirring at room temperature, the methanol is distilled off, and the residue is acidified with 1 M HCl to pH 2-3. It is extracted with ethyl acetate, dried with Na2SO4, and solvent is removed. Recrystallization is carried out from boiling isopropanol. Yield: 830 mg of white solid 4. 0227 1H-NMR (d6-DMSO): 3.57 (s, 2H); 6.92 (d, 1H); 6.99 (tr, 1H); 7.35-7.50 (m, 3H); 8.10 (s, 1H); 8.30 (s, 1H); 9.42 (s, 1H); 12.40 (bs, 1H). 0228 4-Chloro-3-(phenylmethyl)aminocarbonylaminobenzeneacetic Acid 5 0229 2.08 mmol (415 mg) of methyl 3-amino-4-chlorobenzeneacetate is mixed and analogously worked up with 10.4 mmol (969 mg) of aniline as described under 4). Yield: 662 mg of solid. 0230 For ester cleavage, analogously to the above instructions, 2.47 mmol (790 mg) of methyl 4-chloro-3-(phenylmethyl)aminocarbonylaminobenzeneacetate is saponified with 1N-NaOH. Product 5 is obtained without recrystallization. Yield: 693 mg of yellowish solid. 0231 ES-MS: 319 (MH*) 0232 4-Chloro-3-(4-pyridinylamino)carbonylaminobenzeneacetic Acid 6 0233 2.08 mmol (415 mg) of methyl 3-amino-4-chlorobenzeneacetate is mixed and analogously worked up with 10.4 mmol (979 mg) of 4-aminopyridine as described under 4). 0234 Yield: 664 mg of solid. 0235 For ester cleavage, 2.63 mmol (840 mg) of methyl 4-chloro-3-(4-pyridinylamino)carbonylaminobenzeneacetate is saponified with 1N NaOH analogously to the instructions above. Product 6 is obtained without recrystallization. Yield: 481 mg of yellowish solid. 1H-NMR (d6-DMSO): 3.57 (s, 2H); 6.94 (d, 1H); 7.40 (m; 3H); 8.05 (s, 1H); 8.35 (d, 2H); 8.50 (s, 1H); 9.92 (s, 1H); 12.40 (bs, 1H) 0236 4-Chloro-3-(2-pyridinylamino)carbonylaminobenzeneacetic Acid 7 0237 2.08 mmol (415 mg) of methyl 3-amino-4-chlorobenzeneacetate is mixed and analogously worked up with 10.4 mmol (979 ng) of 2-aminopyridine as described under 4.). 0238 Yield: 617 mg of solid. 0239 For ester cleavage, 2.47 mmol (790 mg) of methyl 4-chloro-3-(2-pyridinylamino)carbonylaminobenzeneacetate is saponified with 1N NaOH analogously to the instructions above. Product 7 is obtained without recrystallization. Yield: 693 mg of yellowish solid. 0240 1H-NMR (d6-DMSO): 3.59 (s, 2H); 6.94 (dd, 11H); 7.03 (dd, 1H); 7.22 (d, 1H); 7.42 (d, 1H); 7.78 (dtr, 1H); 8.29 (m, 2H); 10.02 (s, 1H); 11.82 (bs, 1H); 12.50 (s, 1H). 0241 II. Examples of Compounds (I) According to the Invention

Example I 0242 0.3 mmol (42.6 mg) of 4-oxocyclohexanecarboxylic acid is dissolved in 1 ml of acetic acid and added to a suspension of 0.3 mmol (43.3 mg) of phenylhydrazine hydrochloride and 0.3 mmol (40.0 mg) of ZnCl3 in 1 ml of acetic acid. After 20 hours of stirring at 70 C., it is diluted with 20 ml of water and extracted with ethyl acetate. The ethyl acetate phase is washed with water, dried on Na2SO4 and evaporated to the dry state. Yield: 65.6 mg (100%) of white solid. 1NameNumberMgefMcalc2,3,4,9-Tetrahydro-1H-carbazole-3-8215215.2507carboxylic acid

0243 The column headings that are used here also apply to the examples below (Name, Number of the compound, Mgef (determined molecular mass), Mcalc (calculated molecular mass)), which therefore are no longer repeated.

Example 2 0244 The synthesis is carried out on a 0.2 mmol scale according to instructions A, I and O. 22,3,4,9-Tetrahydro-1H-carbazole-3-9214214.2666carboxylic acid amide

Example 3 0245 The synthesis is carried out on a 0.2 mmol scale according to instructions A, F, G, I and O. 3N-(1S)-1-(Aminocarbonyl)-2-methylpropyl-10a314313.3987(3S)-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamideN-(1S)-1-(Aminocarbonyl)-2-methylpropyl-10b314313.3987(3R)-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamideN-(2-Amino-2-oxoethyl)-2,3,4,9-tetrahydro-11271271.31831H-carbazole-3-carboxamide

Example 4 0246 The synthesis is carried out on a 0.2 mmol scale according to instructions D, F, G, F, G, I and O. 4N-(3S)-(2,3,4,9-Tetrahydro-1H-carbazol-3-12a442442.513yl)carbonyl-L-valyl-L-glutamineN-(3R)-(2,3,4,9-Tetrahydro-1H-carbazol-3-12b442442.513yl)carbonyl-L-valyl-L-glutamine, isomer B

Example 5 0247 The synthesis is carried out on a 0.2 mmol scale according to instructions D, F, G, I, F and O: 5N-(3S)-3-Amino-2,3,4,9-tetrahydro-1H-13301301.3441carbazol-3-yl-carbonyl-L-alanine

Example 6 0248 0.1 mmol of carboxylic acid, 0.1 mmol of HOBt, and 0.15 mmol of amine components are dissolved in 15 ml of dry DMF (also THF, DCM), and 0.5 mmol of NMM is added while being cooled with ice and stirred. After about 15 minutes, 0.15 mmol of EDCIHCl is added, it is stirred for one more hour, it is heated to room temperature, and stirring is continued overnight. For working-up, the solvent is drawn off, the product is dissolved in ethyl acetate, and washed twice each with 0.1N HCl and saturated NaCl solution. After the solvent is dried and drawn off, it is recrystallized, if necessary. 69H-Fluoren-9-ylmethyl (3S)-3-(4-14620620.5439bromophenyl)-methylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbamateMethyl N-(3S)-3-(9H-fluoren-9-15537537.6129ylmethoxy)carbonyl-amino-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbonyl-L-alaninate

Example 7 0249 The synthesis is carried out on a 0.2 mmol scale according to instructions A, F, G, F, G, F, G and O. 7N-(3R)-3-(2S,3S)-2-(9H-Fluoren-9-16779777.9178ylmethoxy)-carbonylamino-3-methyl-1-oxopentylamino-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3S)-3-(2S,3S)-2-(9H-Fluoren-9-17779777.9178ylmethoxy)-carbonylamino-3-methyl-1-oxopentylamino-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3R)-2,3,4,9-Tetrahydro-3-(1-oxo-2,3-18651650.7758diphenyl-propyl)amino-1H-carbaol-3-yl-carbonyl-L-valyl-L-aspartamideN-(3S)-2,3,4,9-Tetrahydro-3-(1-oxo-2,3-19651650.7758diphenyl-propyl)amino-1H-carbazol-3-yl-carbonyl-L-valyl-L-aspartamide, isomer AN-(3S)-2,3,4,9-Tetrahydro-3-(1-oxo-2,3-20651650.7758diphenyl-propyl)amino-1H-carbazol-3-yl-carbonyl-L-valyl-L-aspartamide, isomer BN-(3S)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-21688687.8371methyl-1-oxo-2-(1-oxo-3-phenylpropyl)amino-pentylamino-1H-carbazol-3-ylcarbonyl-L-valylL-aspartamideN-(3R)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-22688687.8371methyl-1-oxo-2-(1-oxo-3-phenylpropyl)amino-pentylamino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3S)-2,3,4,9-Tetrahydro-3-(2S)-1-oxo-2-23648647.7289(phenylmethoxy)carbonylaminopropyl-amino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3R)-2,3,4,9-Tetrahydro-3-(2S)-1-oxo-2-24648647.7289(phenylmethoxy)carbonylaminopropyl-amino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3R)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-25662661.7557methyl-1-oxo-2-(phenylmethoxy)carbonyl-aminopentylamino-1H-carbazol-3-ylcarbonyl-L-alanyl-L-aspartamideN-(3R)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-26647646.7844methyl-1-oxo-2-(phenylmethoxy)carbonyl-aminopentylamino-1H-carbazol-3-ylcarbonyl-L-valyl-L-alaninamideN-(3S)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-27690689.8093methyl-1-oxo-2-(phenylmethoxy)carbonyl-aminopentylamino-1H-carbazol-3-ylcarbonyl-D-valyl-L-aspartamideN-(3R)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-28690689.8093methyl-1-oxo-2-(phenylmethoxy)carbonyl-aminopentylamino-1H-carbazol-3-ylcarbonyl-D-valyl-L-aspartamideN-(3R)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-29690689.8093methyl-1-oxo-2-(phenylmethoxy)carbonyl-aminopentylamino-1H-carbazol-3-ylcarbonyl-L-valyl-D-aspartamideN-(3S)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-30690689.8093methyl-1-oxo-2-(phenylmethoxy)carbonyl-aminopentylamino-1H-carbazol-3-ylcarbonyl-L-valyl-D-aspartamideN-(3S)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-31662661.7557methyl-1-oxo-2-(phenylmethoxy)carbonyl-aminopentylamino-1H-carbazol-3-ylcarbonyl-L-alanyl-L-aspartamideN-(3S)-2,3,4,9-Tetrahydro-3-(phenylacetyl)-32651560.6514amino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3R)-2,3,4,9-Tetrahydro-3-(1-oxo-3-33575574.6782phenylpropyl)amino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3S)-2,3,4,9-Tetrahydro-3-(1-oxo-3-34575574.6782phenylpropyl)amino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3S)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-35647646.7844methyl-1-oxo-2-(phenylmethoxy)carbonyl-aminopentylamino-1H-carbazol-3-ylcarbonyl-L-valyl-L-alaninamideN-(3R)-2,3,4,9-Tetrahydro-3-(phenylacetyl)-36561560.6514amino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3R)-2,3,4,9-Tetrahydro-3-(1-oxo-4-37589588.705phenylbutyl)amino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3S)-2,3,4,9-Tetrahydro-3-(1-oxo-4-38589588.705phenylbutyl)amino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3R)-3-(Diphenylacetyl)amino-2,3,4,9-39637636.749tetrahydro-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3S)-3-(Diphenylacetyl)amino-2,3,4,9-40637636.749tetrahydro-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3R)-2,3,4,9-Tetrahydro-3-(1-oxo-2-41575574.6782phenylpropyl)amino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamide, Isomer AN-(3R)-2,3,4,9-Tetrahydro-3-(3-methyl-1-oxo-42617616.75862-phenylpentyl)amino-1H-carbazol-3-yl-carbonyl-L-valyl-L-aspartamide, Isomer BN-(3S)-2,3,4,9-Tetrahydro-3-(3-methyl-1-oxo-43617616.75862-phenylpentyl)amino-1H-carbazol-3-yl-carbonyl-L-valyl-L-aspartamide, Isomer AN-(3S)-2,3,4,9-Tetrahydro-3-(3-methyl-1-oxo-44617616.75862-phenylpentyl)amino-1H-carbazol-3-yl-carbonyl-L-valyl-L-aspartamide, Isomer BPhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-4-45695694.8284(aminocarbonyl)phenylaminocarbonyl-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-46695694.82844-(aminocarbonyl)phenylaminocarbonyl-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methyl-butylcarbamateN-(3S)-2,3,4,9-Tetrahydro-3-(3-methyl-1-oxo-47603602.73182-phenylbutyl)amino-1H-carbazol-3-yl-carbonyl-L-valyl-L-aspartamide, Isomer AN-(3S)-2,3,4,9-Tetrahydro-3-(3-methyl-1-48603602.7318oxo-2-phenylbutyl)amino-1H-carbazol-3-yl-carbonyl-L-valyl-L-aspartamide, Isomer BN-(3R)-2,3,4,9-Tetrahydro-3-(3-methyl-1-oxo-49603602.73182-phenylbutyl)amino-1H-carbazol-3-yl-carbonyl-L-valyl-L-aspartamidePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-50715714.90264-(aminocarbonyl)cyclohexylmethyl-aminocarbonyl-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamateN-(3R)-2,3,4,9-Tetrahydro-3-(3-51653652.748phenoxyphenyl)acetyl-amino-1H-carbazol-3-yl-carbonyl-L-valyl-L-aspartamideN-(3S)-2,3,4,9-Tetrahydro-3-(3-52653652.748phenoxyphenyl)acetyl-amino-1H-carbazol-3-yl-carbonyl-L-valyl-L-aspartamidePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-53709708.85523-(aminocarbonyl)phenylmethylamino-carbonyl-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-54709708.85523-(aminocarbonyl)phenylmethylamino-carbonyl-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamate(3R)-N-(1S)-1-(Aminocarbonyl)-2-55608607.7509methylpropyl-2,3,4,9-tetrahydro-3-(2R)-1-oxo-2-(1-oxo-3-phenylpropyl)-amino-3-phenylpropylamino-1H-carbazole-3-carboxamideN-(3S)-2,3,4,9-Tetrahydro-3-(1-oxo-2-56575574.6782phenylpropyl)-amino-1H-carbazol-3-yl-carbonyl-L-valyl-L-aspartamidePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-57715714.90261-4-(aminocarbonyl)cyclohexylmethyl-aminocarbonyl-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamate

Example 8 0250 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, F, G and O. 8Phenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-58576575.7059(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamateN-(3S)-3(9H-Fluoren-9-ylmethoxy)-59665664.759carbonylamino-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3R)-3-(9H-Fluoren-9-ylmethoxy)-60665664.759carbonylamino-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamidePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-61576575.7059(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-4-62596595.6963(aminocarbonyl)phenylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-4-63596595.6963(aminocarbonyl)phenylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S,2S)-64590589.73271-(aminocarbonyl)-2-methylbutylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S,2S)-65590589.73271-(aminocarbonyl)-2-methylbutylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-2-66623623.7499amino-2-oxo-1-(phenylmethyl)ethylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-2-67623623.7499amino-2-oxo-1-(phenylmethyl)ethylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamate(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-68460460.5748propyl-2,3,4,9-tetrahydro-3-(1-oxo-2-phenyl-propyl)amino-1H-carbazole-3-carboxamidePhenylmethyl (1S,2S)-1-(3S)-3-3-69610609.7231(aminocarbonyl)phenylmethylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-3-70610609.7231(aminocarbonyl)phenylmethylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-4-71615615.7705(aminocarbonyl)cyclohexylmethylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-4-72615615.7705(aminocarbonyl)cyclohexylmethylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-3-73596595.6963(aminocarbonyl)phenylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-3-74596595.6963(aminocarbonyl)phenylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-2-75610609.7231amino-2-oxo-1-phenylethylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1R)-2-76610609.7231amino-2-oxo-1-phenylethylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(2-amino-77609609.72312-oxo-1-phenylethyl)aminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate, Isomer APhenylmethyl (1S,2S)-1-(3R)-3-(2-amino-78609609.72312-oxo-1-phenylethyl)aminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate, Isomer B(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-79462462.547propyl-2,3,4,9-tetrahydro-3-(3-hydroxy-phenyl)acetylamino-1H-carbazole-3-carboxamide(3R)-3-3-(Acetyloxy)phenylacetyl-80504504.5838amino-N-(1S)-1-(aminocarbonyl)-2-methyl-propyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide3-2-(3R)-3-(1S)-1-(Aminocarbonyl)-2-81597596.6804methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-2-oxoethylphenyl 3-hydroxybenzeneacetate(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-82462462.547propyl-2,3,4,9-tetrahydro-3-(hydroxyphenyl-acetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-83525525.4441propyl-3-(4-bromophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-84481480.9931propyl-3-(2-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-85497496.9921propyl-3-(3-chloro-4-hydroxyphenyl)-acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-3-4-(Acetyloxy)-3-chlorophenyl-86539539.0289acetylamino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-87481480.5371propyl-3-(3-fluoro-4-hydroxyphenyl)acetyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-3-4-(Acetyloxy)-3-fluorophenylacetyl-88523522.5739amino-N-(1S)-1-(aminocarbonyl)-2-methyl-propyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-89492491.5451propyl-2,3,4,9-tetrahydro-3-(4-nitrophenyl)-acetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-90515515.4382propyl-3-(2,4-dichlorophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-91464464.5381propyl-3-(4-fluorophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-92462462.547propyl-2,3,4,9-tetrahydro-3-(4-hydroxy-phenyl)acetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-93525525.4441propyl-3-(2-bromophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-94491491.5451propyl-2,3,4,9-tetrahydro-3-(2-nitrophenyl)-acetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-95491491.5451propyl-2,3,4,9-tetrahydro-3-(3-nitrophenyl)-acetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-96525525.4441propyl-3-(3-bromophenyl)acetyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-97499498.9832propyl-3-(2-chloro-4-fluorophenyl)acetyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-98523522.6456propyl-3-(1,1-biphenyl-4-ylacetyl)amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-99475474.6016propyl-3-(3,5-dimethylphenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-100490490.557propyl-3-(1,3-benzodioxol-5-ylacetyl)amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-101481480.9931propyl-3-(3-chlorophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-102461460.5748propyl-2,3,4,9-tetrahydro-3-(3-methyl-phenyl)acetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-103464464.5381propyl-3-(2-fluorophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-104461460.5748propyl-2,3,4,9-tetrahydro-3-(2-methyl-phenyl)acetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-105489488.6284propyl-2,3,4,9-tetrahydro-3-4-(1-methyl-ethyl)phenylacetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-106490489.6165propyl-3-4-(dimethylamino)phenylacetyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-107524524.6388propyl-2,3,4,9-tetrahydro-3-4-(methyl-sulfonyl)phenylacetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-108478478.5649propyl-3-(3-fluoro-4-methylphenyl)acetyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide

Example 9 0251 The synthesis is carried out on a 0.2 mmol-scale according to instructions B, F, G, F, G, F, G and O. 9N-(3R)-2,3,4,9-Tetrahydro-3-(2S,3S)-109691690.79343-methyl-1-oxo-2-(phenylmethoxy)carbonyl-aminopentylamino-1H-carbazol-3-yl-carbonyl-L-valyl-L-asparagineN-(3S)-2,3,4,9-Tetrahydro-3-(2S,3S)-110691690.79343-methyl-1-oxo-2-(phenylmethoxy)carbonyl-aminopentylamino-1H-carbazol-3-yl-carbonyl-L-valyl-L-asparagine

Example 10 0252 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, F, G, F, G, F, H and O. 10N-(3R)-3-(2S,3S)-2-(Acetylamino)-3-111598597.7127methyl-1-oxopentylamino-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3S)-3-(2S,3S)-2-(Acetylamino)-3-112598597.7127methyl-1-oxopentylamino-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3R)-3-(2R,3R)-2-(Acetylamino)-3-113598597.7127methyl-1-oxopentylamino-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3S)-3-(2R,3R)-2-(Acetylamino)-3-114598597.7127methyl-1-oxopentylamino-2,3,4,9-tetrahydro-1H-carbazol-3-oxopentylamino-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamide

Example 11 0253 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, F, G, F, H and O. 11N-(3R)-3-(Acetylamino)-2,3,4,9-tetrahydro-115484484.55381H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3S)-3-(Acetylamino)-2,3,4,9-tetrahydro-116484484.55381H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3S)-3-(Acetylamino)-2,3,4,9-tetrahydro-117484484.55381H-carbazol-3-ylcarbonyl-D-valyl-L-aspartamideN-(3S)-3-(Acetylamino)-2,3,4,9-tetrahydro-118484484.55381H-carbazol-3-ylcarbonyl-L-valyl-D-aspartamide

Example 12 0254 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G and O. 12Phenylmethyl (1S,2S)-1-(3R)-3-119476476.5738(aminocarbonyl)-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-120476476.5738(aminocarbonyl)-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate

Example 13 0255 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, F, G, F, G, F, G and O. 13N-(3R)-2,3,4,9-Tetrahydro-3-(2S)-1-oxo-2-121722721.8543(1-oxo-3-phenylpropyl)amino-3-phenylpropylamino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3R)-2,3,4,9-Tetrahydro-3-2R,3R)-3-122688687.8371methyl-1-oxo-2-(1-oxo-3-phenylpropyl)aminopentylamino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamide

Example 14 0256 The synthesis is carried out on a 0.2 mmol-scale according to instructions D, F, G, F, G and O. 14N-(3R)-2,3,4,9-Tetrahydro-3-(2S,38)-3-123577576.69methyl-1-oxo-2-(phenylmethoxy)carbonylaminopentylamino-1H-carbazol-3-ylcarbonyl-L-valine, N-(3R)-2,3,4,9-Tetrahydro-3-(2S)-3-methyl-1-oxo-2-(phenylmethoxy)carbonylaminopentylamino-1H-carbazol-3-ylcarbonyl-L-valineN-(3S)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-124577576.69methyl-1-oxo-2-(phenylmethoxy)carbonylaminopentylamino-1H-carbazol-3-ylcarbonyl-L-valine

Example 15 0257 The synthesis is carried out on a 0.2 mmol-scale according to instructions C, F, G, F, G, F, G and P. 15N-(3R)-3-(2S,3S)-2-(1,1-Dimethylethoxy)-125656655.7921carbonylamino-3-methyl-1-oxopentylamino-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamide

Example 16 0258 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, F, G, F and O. 16N-(3S)-3-Amino-2,3,4,9-tetrahydro-1H-126442442.517carbazol-3-ylcarbonyl-L-valyl-L-aspartamideN-(3R)-3-Amino-2,3,4,9-tetrahydro-1H-127442442.517carbazol-3-ylcarbonyl-L-valyl-L-aspartamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-128441441.5725propyl-3-(2S,3S)-2-amino-3-methyl-1-oxopentylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide

Example 17 0259 The synthesis is carried out on a 0.2 mmol-scale according to instructions D, F, G, F, G, F, H and O. 17N-(3S)-3-(Acetylamino)-2,3,4,9-tetrahydro-129435485.53791H-carbazol-3-ylcarbonyl-L-valyl-L-asparagine

Example 18 0260 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, F, H and O. 18(3R)-3-(Acetylamino)-N-(1S)-2-amino-2-oxo-130418418.49441-(phenylmethyl)ethyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-2-amino-2-oxo-131418418.49441-(phenylmethyl)ethyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide

Example 19 0261 The synthesis is carried out on a 0.2 mmol-scale according to instructions B, F, G and O. 19(3S)-2,3,4,9-Tetrahydro-3-2S,3S)-3-methyl-132478477.55791-oxo-2-(phenylmethoxy)carbonylaminopentylamino-1H-carbazole-3-carboxylic acid

Example 20 0262 The synthesis is carried out on a 0.2 mmol-scale according to instructions B, F, G, F and O. 20(3S)-3-(2,2-Diphenylethyl)aminoacetyl-134468467.5661amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid

Example 21 0263 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, F, H and O. 21(3S)-3-(Acetylamino)-N-3-135404404.4676(aminocarbonyl)phenyl-methyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-4-136410410.515(aminocarbonyl)cyclohexyl-methyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-3-(Acetylamino)-N-4-137410410.515(aminocarbonyl)cyclohexyl-methyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-2-amino-2-oxo-138404404.46761-phenylethyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide

Example 22 0264 The synthesis is carried out on a 0.2 mmol-scale according to Examples 18 and 6. 22Phenylmethyl (1S,2S)-1-(3R)-3-139505504.6274(ethylamino)carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-2-methyl-1-(3R)-140519518.65422,3,4,9-tetrahydro-3-(1-methylethyl)amino-carbonyl-1H-carbazol-3-ylaminocarbonyl-butylcarbamatePhenylmethyl (1S,2S)-2-methyl-1-(3R)-141533532.6812,3,4,9-tetrahydro-3-(2-methylpropyl)amino-carbonyl-1H-carbazol-3-ylaminocarbonyl-butylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-2,2-142547546.7078dimethylpropyl)aminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-2-methyl-1-(3R)-143553552.67142,3,4,9-tetrahydro-3-(phenylamino)carbonyl-1H-carbazol-3-ylaminocarbonylbutyl-carbamatePhenylmethyl (1S,2S)-2-methyl-1-(3R)-144567566.69822,3,4,9-tetrahydro-3-(phenylmethyl)amino-carbonyl-1H-carbazol-3-ylaminocarbonyl-butylcarbamatePhenylmethyl (1S,2S)-2-methyl-1-(3R)-145581580.7252,3,4,9-tetrahydro-3-(2-phenylethyl)amino-carbonyl-1H-carbazol-3-ylaminocarbonyl-butylcarbamatePhenylmethyl (1S,2S)-2-methyl-1-(3R)-146595594.75182,3,4,9-tetrahydro-3-(3-phenylpropyl)amino-carbonyl-1H-carbazol-3-ylaminocarbonyl-butylcarbamate

Example 23 0265 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, I, F, G and O. 23Phenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-147a606605.7317(aminocarbonyl)-2-methypropylamino-carbonyl-2,3,4,9-tetrahydro-8-methoxy-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-147b606605.7317(aminocarbonyl)-2-methy-propylamino-carbonyl-2,3,4,9-tetrahydro-8-methoxy-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-148a610610.151(aminocarbonyl)-2-methylpropylamino-carbonyl-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-148b610610.151(aminocarbonyl)-2-methylpropylamino-carbonyl-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-180a610610.151(aminocarbonyl)-2-methylpropylamino-carbonyl-8-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-180b610610.151(aminocarbonyl)-2-methylpropylamino-carbonyl-8-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-149a644643.703(aminocarbonyl)-2-methypropylamino-carbonyl-2,3,4,9-tetrahydro-8-(trifluoro-methyl)-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-149b644643.703(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-8-(trifluoro-methyl)-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-150a590589.7327(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-8-methyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-150b590589.7327(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-8-methyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-151a590589.7327(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-5-methyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-151b590589.7327(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-5-methyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-151c590589.7327(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-7-methyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-151d590589.7327(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-7-methyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-152a610610.151(aminocarbonyl)-2-methylpropylamino-carbonyl-5-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-152b610610.151(aminocarbonyl)-2-methylpropylamino-carbonyl-7-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-152c610610.151(aminocarbonyl)-2-methy-propylamino-carbonyl-7-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate(3R)-3-(1S)-1-(Aminocarbonyl)-2-methyl-153a620619.7149propyl-aminocarbonyl-2,3,4,9-tetrahydro-3-(2S,3S)-3-methyl-1-oxo-2-(phenyl-methoxy)carbonylaminopentylamino-1H-carbazole-8-carboxylic acid(3S)-3-(1S)-1-(Aminocarbonyl)-2-methyl-153b620619.7149propyl-aminocarbonyl-2,3,4,9-tetrahydro-3-(2S,3S)-3-methyl-1-oxo-2-(phenyl-methoxy)carbonylaminopentylamino-1H-carbazole-8-carboxylic acidPhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-154a593593.696(aminocarbonyl)-2-methylpropylamino-carbonyl-6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-154b593593.696(aminocarbonyl)-2-methylpropylamino-carbonyl-6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-155a605605.7317(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-6-methoxy-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-155b605605.7317(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-6-methoxy-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-156a589589.7327(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-6-methyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-156b589589.7327(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-6-methyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-157a621620.703(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-6-nitro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-157b621620.703(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-6-nitro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-158633632.7616(aminocarbonyl)-4-(aminoiminomethyl)-aminobutylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-159a447447.5361propyl-2,3,4,9-tetrahydro-3-(3-pyridinyl-acetyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-159b447447.5361propyl-2,3,4,9-tetrahydro-3-(3-pyridinyl-acetyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-160a496496.6078propyl-2,3,4,9-tetrahydro-3-(1-naphthalenyl-acetyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-160b496496.6078propyl-2,3,4,9-tetrahydro-3-(1-naphthalenyl-acetyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-161a496496.6078propyl-2,3,4,9-tetrahydro-3-(2-naphthalenyl-acetyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-161b496496.6078propyl-2,3,4,9-tetrahydro-3-(2-naphthalenyl-acetyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-162a472472.5858propyl-3-(2,3-dihydro-1H-inden-1-yl)-carbonylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-162b472472.5858propyl-3-(2,3-dihydro-1H-inden-1-yl)-carbonylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-163a436436.5132propyl-2,3,4,9-tetrahydro-3-(1H-imidazol-4-ylacetyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-163b436436.5132propyl-2,3,4,9-tetrahydro-3-(1H-imidazol-4-ylacetyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-164a486485.5849propyl-2,3,4,9-tetrahydro-3-(1H-indol-3-yl-acetyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-164b486485.5849propyl-2,3,4,9-tetrahydro-3-(1H-indol-3-yl-acetyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-165a461460.5748propyl-2,3,4,9-tetrahydro-3-(4-methyl-phenyl)acetylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-165b461460.5748propyl-2,3,4,9-tetrahydro-3-(4-methyl-phenyl)acetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-166a515514.5451propyl-2,3,4,9-tetrahydro-3-4-(trifluoromethyl)phenylacetylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-166b515514.5451propyl-2,3,4,9-tetrahydro-3-4-(trifluoromethyl)phenylacetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-167a481480.9931propyl-3-(4-chlorophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-167b481480.9931propyl-3-(4-chlorophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-168a515514.5451propyl-2,3,4,9-tetrahydro-3-3-(trifluoro-methyl)phenylacetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-168b515514.5451propyl-2,3,4,9-tetrahydro-3-3-(trifluoro-methyl)phenylacetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-169a465464.5381propyl-3-(3-fluorophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-169b465464.5381propyl-3-(3-fluorophenyl)acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-170a477476.5738propyl-2,3,4,9-tetrahydro-3-(3-methoxy-phenyl)acetylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-170b477476.5738propyl-2,3,4,9-tetrahydro-3-(3-methoxy-phenyl)acetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-171a477476.5738propyl-2,3,4,9-tetrahydro-3-(2-methoxy-phenyl)acetylamino1H-carbazole-3-carboxamide-(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-171b477476.5738propyl-2,3,4,9-tetrahydro-3-(2-methoxy-phenyl)acetylamino1H-carbazole-3-carboxamide-(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-172a479478.5649propyl-3-3-(4-fluorophenyl)-1-oxopropyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-172b479478.5649propyl-3-3-(4-fluorophenyl)-1-oxopropyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-173a497496.555propyl-3-3-(3,4-difluorophenyl)-1-oxoprop-ylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-173b497496.555propyl-3-3-(3,4-difluorophenyl)-1-oxoprop-ylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-174a593592.6057propyl-3-3-3,4-bis(trifluoromethyl)phenyl-1-oxopropylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methylprop-174b593592.6057yl-3-3-3,4-bis(trifluoromethyl)phenyl-1-oxopropylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamideN-(1S)-1-(Aminocarbonyl)-2-methylpropyl-175477476.57382,3,4,9-tetrahydro-3-(4-methoxyphenyl)-acetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-176a491490.6006propyl-2,3,4,9-tetrahydro-3-3-(4-methoxy-phenyl)-1-oxopropylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-176b491490.6006propyl-2,3,4,9-tetrahydro-3-3-(4-methoxy-phenyl)-1-oxopropylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-177a491490.6006propyl-2,3,4,9-tetrahydro-3-3-(2-methoxy-phenyl)-1-oxopropylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-177b491490.6006propyl-2,3,4,9-tetrahydro-3-3-(2-methoxy-phenyl)-1-oxopropylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-178a500499.6117propyl-2,3,4,9-tetrahydro-3-3-(1H-indol-3-yl)-1-oxopropylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-178b500499.6117propyl-2,3,4,9-tetrahydro-3-3-(1H-indol-3-yl)-1-oxopropylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-179a503502.6552propyl-2,3,4,9-tetrahydro-3-(1-oxo-6-phenyl-hexyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-179b503502.6552propyl-2,3,4,9-tetrahydro-3-(1-oxo-6-phenyl-hexyl)amino-1H-carbazole-3-carboxamidePhenylmethyl (1S,2S)-1-(3R)-3-(2S)-2-181a574573.6901(aminocarbonyl)-1-pyrrolidinylcarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(2S)-2-181b574573.6901(aminocarbonyl)-1-pyrrolidinylcarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylamino-carbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-182a645644.5961(aminocarbonyl)-2-methylpropylamino-carbonyl-7,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-182b645644.5961(aminocarbonyl)-2-methylpropylamino-carbonyl-7,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-183a604603.7595(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-5,8-dimethyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-183b604603.7595(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-5,8-dimethyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-184a645644.5961(aminocarbonyl)-2-methylpropylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-184b645644.5961(aminocarbonyl)-2-methylpropylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-185a655654.602(aminocarbonyl)-2-methylpropylamino-carbonyl-6-bromo-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-185b655654.602(aminocarbonyl)-2-methylpropylamino-carbonyl-6-bromo-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamate(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-186a511511.0189propyl-3-(4-chlorophenyl)acetylamino-2,3,4,9-tetrahydro-8-methoxy-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-186b511511.0189propyl-3-(4-chlorophenyl)acetylamino-2,3,4,9-tetrahydro-8-methoxy-1H-carbazole-3-carboxamidePhenylmethyl (1S,2S)-1-(3R)-3-(1R)-2-187a658658.195amino-1-(4-chlorophenyl)methyl-2-oxoethyl-aminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1R)-2-187b658658.195amino-1-(4-chlorophenyl)methyl-2-oxoethyl-aminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-3-(3-amino-3-188548547.6523oxopropyl)aminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methyl-butylcarbamate(2S)-1-(3R)-3-(4-Chlorophenyl)acetyl-189a509509.0031amino-2,3,4,9-tetrahydro-8-methoxy-1H-carbazol-3-ylcarbonyl-2-pyrrolidine-carboxamide(2S)-1-(3S)-3-(4-Chlorophenyl)acetyl-189b509509.0031amino-2,3,4,9-tetrahydro-8-methoxy-1H-carbazol-3-ylcarbonyl-2-pyrrolidine-carboxamidePhenylmethyl (1S,2S)-1-(3R)-3-(2S)-2-190a628627.7815(aminocarbonyl)octahydro-1H-indol-1-yl-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(2S)-2-190b628627.7815(aminocarbonyl)octahydro-1H-indol-1-yl-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(2S,4R)-2-191a590589.6891(aminocarbonyl)-4-hydroxy-1-pyrrolidinyl-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(2S,4R)-2-191b590589.6891(aminocarbonyl)-4-hydroxy-1-pyrrolidinyl-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S,2R)-291a578577.67811-(aminocarbonyl)-2-hydroxypropylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S,2R)-291b578577.67811-(aminocarbonyl)-2-hydroxypropylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl-aminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(2-amino-292534533.62552-oxoethyl)aminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methyl-butylcarbamatePhenylmethyl (1S,2S)-1-3-2-(amino-192596595.6963carbonyl)phenyl-aminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-193a616616.119propyl-3-4-chloro-3-(4-pyridinyl-amino)-carbonylaminophenyl-acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-193b616616.119propyl-3-4-chloro-3-(4-pyridinyl-amino)carbonylamino-phenyl-acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-194a615615.13propyl-3-4-chloro-3-(phenylamino)-carbonylaminophenyl-acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-194b615615.13propyl-3-4-chloro-3-(phenylamino)-carbonylaminophenylacetyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-195a629629.157propyl-3-4-chloro-3-(phenylmethyl)-amino-carbonylaminophenyl-acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-195b629629.157propyl-3-4-chloro-3-(phenylmethyl)-aminocarbonylamino-phenylacetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-196a616616.119propyl-3-4-chloro-3-(2-pyridinyl-amino)carbonylamino-phenylacetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-196b616616.119propyl-3-4-chloro-3-(2-pyridinyl-amino)carbonylaminophenyl-acetyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide

Example 24 0266 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, I, F, H and O. 24(3R)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-197a400400.4762yl)-2-methylpropyl-2,3,4,9-tetrahydro-8-methoxy-1H-carbazole-methylpropyl-2,3,4,9-tetrahydro-8-methoxy-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-197b400400.4762yl)-2-methylpropyl-2,3,4,9-tetrahydro-8-methoxy-1H-carbazole-3-carboxamide3-(Acetylamino)-N-(1S)-1-(aminocarbonyl)-2-198405404.8955methylpropyl-6-chloro-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide3-(Acetylamino)-N-(1S)-1-(aminocarbonyl)-2-199769768.9544methylpropyl-2,3,4,9-tetrahydro-5-methyl-1H-carbazole-3-carboxamide3-(Acetylamino)-N-(1S)-1-(aminocarbonyl)-2-200769768.9544methylpropyl-2,3,4,9-tetrahydro-8-methyl-1H-carbazole-3-carboxamide3-(Acetylamino)-N-(1S)-1-(aminocarbonyl)-2-201810809.7911methylpropyl-5-chloro-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide3-(Acetylamino)-N-(1S)-1-(aminocarbonyl)-2-202810809.7911methylpropyl-7-chloro-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-203a388388.4405yl)-2-methylpropyl-6-fluoro-2,3,4,9-tetra-hydro-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-203b388388.4405yl)-2-methylpropyl-6-fluoro-2,3,4,9-tetra-hydro-1H-carbazole-3-carboxamide(3R)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-204a400400.4762yl)-2-methylpropyl-2,3,4,9-tetrahydro-6-methoxy-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-204b400400.4762yl)-2-methylpropyl-2,3,4,9-tetrahydro-6-methoxy-1H-carbazole-3-carboxamide(3R)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-205a384384.4772yl)-2-methylpropyl-2,3,4,9-tetrahydro-6-methyl-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-205b384384.4772yl)-2-methylpropyl-2,3,4,9-tetrahydro-6-methyl-1H-carbazole-3-carboxamide(3R)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-206a370370.4504yl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-206b370370.4504yl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-207a439439.3406yl)-2-methylpropyl-7,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-207b439439.3406yl)-2-methylpropyl-7,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-208a399398.504yl)-2-methylpropyl-2,3,4,9-tetrahydro-5,8-dimethyl-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-208b399398.504yl)-2-methylpropyl-2,3,4,9-tetrahydro-5,8-dimethyl-1H-carbazole-3-carboxamide(3R)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-209a439439.3406yl)-2-methylpropyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-(aminocarbon-209b439439.3406yl)-2-methylpropyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide

Example 25 0267 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, I, F, G, F and O. 25(3R)-3-(2S)-2-Amino-5-(aminoiminometh-210a485484.6014yl)amino-1-oxopentylamino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetra-hydro-1H-carbazole-3-carboxamide(3S)-3-(2S)-2-Amino-5-(aminoiminometh-210b485484.6014yl)amino-1-oxopentylamino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetra-hydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-211a497496.652propyl-2,3,4,9-tetrahydro-3-2-(1-piperidin-yl)ethylaminoacetylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-211b497496.652propyl-2,3,4,9-tetrahydro-3-2-(1-piperidin-yl)ethylaminoacetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-212a529528.6534propyl-2,3,4,9-tetrahydro-3-2-(1H-indol-3-yl)ethylaminoacetylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methylprop-212b529528.6534yl-2,3,4,9-tetrahydro-3-2-(1H-indol-3-yl)-ethylaminoacetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-213a520519.5987propyl-3-(1,3-benzodioxol-5-ylmethyl)-aminoacetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methylprop-213b520519.5987yl-3-(1,3-benzodioxol-5-ylmethyl)amino-acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-214a566565.7141propyl-3-(2,2-diphenylethyl)amino-acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methyl-214b566565.7141propyl-3-(2,2-diphenylethyl)amino-acetylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-methyl-215a533532.685propyl-2,3,4,9-tetrahydro-3-2-methyl-(phenylmethyl)aminoethylaminoacetyl-amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-methylprop-215b533532.685yl-2,3,4,9-tetrahydro-3-2-methyl-(phenylmethyl)aminoethylaminoacetyl-amino-1H-carbazole-3-carboxamide

Example 26 0268 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, I, F, G, F, H and O. 263-Acetyl2-(1-216539538.6888piperidinyl)ethylaminoacetylamino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-3-Acetyl2-217a575574.7217methyl(phenylmethyl)aminoethyl-aminoacetylamino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-3-Acetyl2-217b575574.7217methyl(phenylmethyl)aminoethyl-aminoacetylamino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-3-Acetyl(2,2-218a608607.7509diphenylethyl)aminoacetylamino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-3-Acetyl(2,2-218b608607.7509diphenylethyl)aminoacetylamino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-3-Acetyl(1,3-benzodioxol-5-219a562561.6355ylmethyl)aminoacetyl-amino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-3-Acetyl(1,3-benzodioxol-5-219b562561.6355ylmethyl)aminoacetyl-amino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-3-Acetyl2-(1H-indol-3-220a571570.6902yl)ethylaminoacetyl-amino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-3-Acetyl2-(1H-indol-3-220b571570.6902yl)ethylaminoacetyl-amino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide3-(2S)-2-(Acetylamino)-5-221527526.6382(aminoiminomethyl)amino-1-oxopentylamino-N-(1S)-1-(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide

Example 27 0269 The synthesis is carried out on a 0.2 mmol-scale according to instructions C, F, G, I, F, G and P. 27Phenylmethyl (1S,2S)-2-methyl-1-(3R)-222a589589.73272,3,4,9-tetrahydro-3-(1S)-2-methyl-1-(methylamino)carbonyl-propylaminocarbonyl-1H-carbazol-3-ylaminocarbonyl-butylcarbamatePhenylmethyl (1S,2S)-2-methyl-1-(3S)-222b589589.73272,3,4,9-tetrahydro-3-(1S)-2-methyl-1-(methylamino)carbonyl-propylaminocarbonyl-1H-carbazol-3-ylamino-carbonylbutylcarbamate

Example 28 0270 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, I, F, J and O. 28(3R)-N-(1S)-1-(Aminocarbonyl)-2-223a503503.0203methylpropyl-3-(4-chlorophenyl)sulfonylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-223b503503.0203methylpropyl-3-(4-chlorophenyl)sulfonylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-224a407406.5044methylpropyl-2,3,4,9-tetrahydro-3-(methylsulfonyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-224b407406.5044methylpropyl-2,3,4,9-tetrahydro-3-(methylsulfonyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-225a469468.5752methylpropyl-2,3,4,9-tetrahydro-3-(phenylsulfonyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-225b469468.5752methylpropyl-2,3,4,9-tetrahydro-3-(phenylsulfonyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-226a483482.602methylpropyl-2,3,4,9-tetrahydro-3-(phenylmethyl)sulfonylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-226b483482.602methylpropyl-2,3,4,9-tetrahydro-3-(phenylmethyl)sulfonylamino-1H-carbazole-3-carboxamide

Example 29 0271 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, I, F, L and O. 293-Phenylpropyl (3R)-3-(1S)-1-227a491490.6006(aminocarbonyl)-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbamate3-Phenylpropyl (3S)-3-(1S)-1-227b491490.6006(aminocarbonyl)-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbamatePhenylmethyl (3R)-3-(1S)-1-228a463462.547(aminocarbonyl)-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbamatePhenylmethyl (3S)-3-(1S)-1-228b463462.547(aminocarbonyl)-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbamatePhenyl (3R)-3-(1S)-1-(aminocarbonyl)-2-229a449448.5202methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbamatePhenyl (3S)-3-(1S)-1-(aminocarbonyl)-2-229b449448.5202methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbamate

Example 30 0272 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, I, F, M and O. 30(3R)-N-(1S)-1-(Aminocarbonyl)-2-230a464463.5351methylpropyl-2,3,4,9-tetrahydro-3-(4-nitrophenyl)methylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-230b464463.5351methylpropyl-2,3,4,9-tetrahydro-3-(4-nitrophenyl)methylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-231a356356.4672methylpropyl-3-(ethylamino)-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-231b356356.4672methylpropyl-3-(ethylamino)-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-232a433432.5648methylpropyl-2,3,4,9-tetrahydro-3-(2-phenylethyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-232b433432.5648methylpropyl-2,3,4,9-tetrahydro-3-(2-phenylethyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-233a447446.5916methylpropyl-2,3,4,9-tetrahydro-3-(3-phenylpropyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-233b447446.5916methylpropyl-2,3,4,9-tetrahydro-3-(3-phenylpropyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-233c565564.7696methylpropyl-3-bis(3-phenylpropyl)amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-234a489488.672methylpropyl-2,3,4,9-tetrahydro-3-(6-phenylhexyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-234b489488.672methylpropyl-2,3,4,9-tetrahydro-3-(6-phenylhexyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-235a370370.494methylpropyl-2,3,4,9-tetrahydro-3-(1-methylethyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-235b370370.494methylpropyl-2,3,4,9-tetrahydro-3-(1-methylethyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-236a385384.5208methylpropyl-2,3,4,9-tetrahydro-3-(1-methylpropyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-236b385384.5208methylpropyl-2,3,4,9-tetrahydro-3-(1-methylpropyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-237a399398.5476methylpropyl-2,3,4,9-tetrahydro-3-(3-methylbutyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-237b399398.5476methylpropyl-2,3,4,9-tetrahydro-3-(3-methylbutyl)amino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-238a342342.4404methylpropyl-2,3,4,9-tetrahydro-3-(methylamino)-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-238b342342.4404methylpropyl-2,3,4,9-tetrahydro-3-(methylamino)-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-238c356356.4672methylpropyl-3-(dimethylamino)-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-238d356356.4672methylpropyl-3-(dimethylamino)-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide

Example 31 0273 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, I, F, K and O. 31(3R)-N-(1S)-1-(Aminocarbonyl)-2-239a385385.4653methylpropyl-2,3,4,9-tetrahydro-3-(methylamino)carbonylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-239b385385.4653methylpropyl-2,3,4,9-tetrahydro-3-(methylamino)carbonylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-240a448447.5361methylpropyl-2,3,4,9-tetrahydro-3-(phenylamino)carbonylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-240b448447.5361methylpropyl-2,3,4,9-tetrahydro-3-(phenylamino)carbonylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-241a462461.5629methylpropyl-2,3,4,9-tetrahydro-3-(phenylmethyl)aminocarbonylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-241b462461.5629methylpropyl-2,3,4,9-tetrahydro-3-(phenylmethyl)aminocarbonylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-242a476475.5897methylpropyl-2,3,4,9-tetrahydro-3-(2-phenylethyl)aminocarbonylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-242b476475.5897methylpropyl-2,3,4,9-tetrahydro-3-(2-phenylethyl)aminocarbonylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-243a454453.5835methylpropyl-3-(cyclohexylamino)carbonyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-243b454453.5835methylpropyl-3-(cyclohexylamino)carbonyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-244a414413.5189methylpropyl-2,3,4,9-tetrahydro-3-(1-methylethyl)aminocarbonylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-244b414413.5189methylpropyl-2,3,4,9-tetrahydro-3-(1-methylethyl)aminocarbonylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-245a428427.5457methylpropyl-2,3,4,9-tetrahydro-3-(1-methylpropyl)aminocarbonylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-245b428427.5457methylpropyl-2,3,4,9-tetrahydro-3-(1-methylpropyl)aminocarbonylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-246a476475.5897methylpropyl-2,3,4,9-tetrahydro-3-(1R)-1-phenylethylaminocarbonylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-246b476475.5897methylpropyl-2,3,4,9-tetrahydro-3-(1R)-1-phenylethylaminocarbonylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-247a482481.9812methylpropyl-3-(4-chlorophenyl)amino-carbonylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-247b482481.9812methylpropyl-3-(4-chlorophenyl)amino-carbonylamino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-248a476475.5897methylpropyl-2,3,4,9-tetrahydro-3-(1S)-1-phenylethylaminocarbonylamino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-248b476475.5897methylpropyl-2,3,4,9-tetrahydro-3-(1S)-1-phenylethylaminocarbonylamino-1H-carbazole-3-carboxamide

Example 32 0274 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, I, F, G, N and O. 32Ethyl (3R)-3-(1S)-1-(aminocarbonyl)-2-249a567567.0825methylpropylaminocarbonyl-3-(4-chlorophenyl)acetylamino-1,2,3,4-tetrahydro-9H-carbazole-9-acetateEthyl (3S)-3-(1S)-1-(aminocarbonyl)-2-249b567567.0825methylpropylaminocarbonyl-3-(4-chlorophenyl)acetylamino-1,2,3,4-tetrahydro-9H-carbazole-9-acetate(3R)-N-(1S)-1-(Aminocarbonyl)-2-250a599599.1711methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-9-(3-phenylpropyl)-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-250b599599.1711methylpropyl-3-(4-chlorophenyl)-acetylamino-2,3,4,9-tetrahydro-9-(3-phenylpropyl)-1H-carbazole-3-carboxamide(3R)-3-(1S)-1-(Aminocarbonyl)-2-251a539539.0289methylpropyl-aminocarbonyl-3-(4-chlorophenyl)acetylamino-1,2,3,4-tetrahydro-9H-carbazole-9-acetic acid(3S)-3-(1S)-1-(Aminocarbonyl)-2-251b539539.0289methylpropylaminocarbonyl-3-(4-chlorophenyl)acetylamino-1,2,3,4-tetrahydro-9H-carbazole-9-acetic acid(3R)-N-(1S)-1-(Aminocarbonyl)-2-252a551551.1271methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-9-(3-methylbutyl)-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-252b551551.1271methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-9-(3-methylbutyl)-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-253a572572.1056methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-9-(4-pyridinylmethyl)-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-253b572572.1056methylpropyl-3-(4-chlorophenyl)-acetylamino-2,3,4,9-tetrahydro-9-(4-pyridinylmethyl)-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-254a572572.1056methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-9-(3-pyridinylmethyl)-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-254b572572.1056methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-9-(3-pyridinylmethyl)-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-255a621621.1773methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-9-(2-naphthalenylmethyl)-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-255b621621.1773methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-9-(2-naphthalenylmethyl)-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-256a537537.1003methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-9-(2-methylpropyl)-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-256b537537.1003methylpropyl-3-(4-chlorophenyl)-acetylamino-2,3,4,9-tetrahydro-9-(2-methylpropyl)-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-257a585585.1443methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-9-(2-phenylethyl)-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-257b585585.1443methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-9-(2-phenylethyl)-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-258a509509.0467methylpropyl-3-(4-chlorophenyl)-acetylamino-9-ethyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-258b509509.0467methylpropyl-3-(4-chlorophenyl)-acetylamino-9-ethyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-259a577577.1649methylpropyl-3-(4-chlorophenyl)acetyl-amino-9-(cyclohexylmethyl)-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-259b577577.1649methylpropyl-3-(4-chlorophenyl)acetyl-amino-9-(cyclohexylmethyl)-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-260a607607.0977methylpropyl-3-(4-chlorophenyl)acetyl-amino-9-(2,6-difluorophenyl)methyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-260b607607.0977methylpropyl-3-(4-chlorophenyl)acetyl-amino-9-(2,6-difluorophenyl)methyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide

Example 33 0275 The synthesis is carried out on a 0.2 mmol-scale according to instructions A, F, G, I, F, H, N and O. 33(3R)-3-(Acetylamino)-N-(1S)-1-261a489488.6284(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-9-(3-phenylpropyl)-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-261b489488.6284(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-9-(3-phenylpropyl)-1H-carbazole-3-carboxamide(3R)-3-(Acetylamino)-N-(1S)-1-262a441440.5844(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-9-(3-methylbutyl)-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-262b441440.5844(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-9-(3-methylbutyl)-1H-carbazole-3-carboxamide(3R)-3-(Acetylamino)-N-(1S)-1-263a511510.6346(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-9-(2-naphthalenylmethyl)-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-263b511510.6346(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-9-(2-naphthalenylmethyl)-1H-carbazole-3-carboxamide3-(Acetylamino)-N-(1S)-1-264511510.6346(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-9-(1-naphthalenylmethyl)-1H-carbazole-3-carboxamide3-(Acetylamino)-N-(1S)-1-265467466.6222(aminocarbonyl)-2-methylpropyl-9-(cyclohexylmethyl)-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-3-(Acetylamino)-N-(1S)-1-266a427426.5576(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-9-(2-methylpropyl)-1H-carbazole-3-carboxamide(3S)-3-(Acetylamino)-N-(1S)-1-266b427426.5576(aminocarbonyl)-2-methylpropyl-2,3,4,9-tetrahydro-9-(2-methylpropyl)-1H-carbazole-3-carboxamide

Example 34 0276 The synthesis is carried out on a 0.2 mmol-scale according to instructions D, F, G, I, F, O and subsequent coupling according to Example 6. 34Phenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-267a563562.7068(hydroxymethyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3S)-3-(1S)-1-267b563562.7068(hydroxymethyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate

Example 35 0277 Ethyl 2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazole-3-carboxylate 268 0278 10 mmol (1.6 ml) of ethyl 4-oxocyclohexanecarboxylate, 25 mmol (1.4 ml) of glycol and 10 mol of pTsOH are refluxed for 24 hours in dry toluene in a water separator. Solvent is removed and taken up in ethyl acetate/water. The organic phase is washed with water, dried and evaporated to the dry state. The product is distilled under high vacuum at 120 C. and 0.03 mbar in the ball tube still. 0279 Yield: 1.52 g of 4-ethyl 1,4-dioxaspiro4,5decane-8-carboxylate 269. 0280 85 l of diisopropylamine in 500 l of dry THF is added in drops to 0.6 mmol of a 1.6 molar solution of butyllithium in heptane at 20 C. under argon, and it is stirred for 10 more minutes. After cooling to 70 C., 0.5 mmol (107 mg) of 269 in 200 l of dry THF is added in drops, allowed to reach 0 C. within one hour, and stirred for another 30 minutes. After cooling to 70 C., 0.7 mmol (106 l) of 1-bromo-3-phenylpropane in 300 l of dry THF is added, and it is stirred for 30 more minutes. It is allowed to reach room temperature and stirred for one more hour. The organic phase is carefully mixed with saturated NH4Cl solution and n-hexane, and it is stirred for 10 minutes. The organic phase is separated and washed with water. After filtration with a Whatman filter, it is evaporated to the dry state. 0281 Yield: 165 mg of ethyl 8-(3-phenylpropyl)-1,4-dioxaspiro4,5decane-8-carboxylate 270. 0282 0.6 mmol (200 mg) of 270 is taken up in 25 ml of acetone/0.1 M HCl 1:1 and stirred with catalytic amounts of pTsOH for 48 hours at 50 C. The acetone is drawn off in a rotary evaporator, and the precipitated product is filtered off, rewashed with water and dried. 0283 Yield: 156 mg of ethyl 4-oxo-8-(3-phenylpropyl)cyclohexanecarboxylate 271. 0284 The indolization is carried out as described under Example 1 with phenylhydrazine. 0285 The yield after evaporation and preparative HPLC: 65 mg of ethyl 2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazole-3-carboxylate 268. 0286 ES-MS: 362 (MH) 0287 80 mg of ethyl 6,8-dichloro-2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazole-3-carboxylate 272 is produced analogously with use of 2,4-dichlorophenylhydrazine. 0288 ES-MS: 430 (MH)

Example 36 0289 2,3,4,9-Tetrahydro-3-(3-phenylpropyl)-1H-carbazole-3-carboxylic Acid 273 0290 3.94 mmol (1.31 g) of 269 is stirred in 50 ml of methanol and 30 ml of 50% sodium hydroxide solution for 4 hours at 60 C. It is acidified with dilute HCl and extracted with ether. Drying with Na2SO4 and evaporation yields 1.02 g (85%) of white solid 8-(3-phenylpropyl)-1,4-dioxaspiro4,5decane-8-carboxylic acid 274. 0291 65 mg of 274 is first deprived of protection with HCl as described for 270 and 271 and then reacted with phenylhydrazine for indolization. 0292 Yield after evaporation and preparative HPLC: 15 mg of 273. 0293 ES-MS: 334 (MH) 0294 39 mg of 6,8-dichloro-2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazole-3-carboxylic acid 275 is produced analogously with use of 2,4-dichlorophenylhydrazine. 0295 ES-MS: 478 (MH)

Example 37 0296 2,3,4,9-Tetrahydro-N-(1S)-1-(hydroxymethyl)-2-methylpropyl-3-(3-phenylpropyl)-1H-carbazole-3-carboxamide 276 0297 0.66 mmol (200 mg) of 274 is reacted analogously to Example 6 with 1.5 equivalents of valinol. 277 mg of white solid N-(1S)-1-(hydroxymethyl)-2-methylpropyl-8-(3-phenylpropyl)-1,4-dioxaspiro 4,5decane-8-carboxamide 277 is obtained. 0298 Then, as described for 270 and 271, 0.3 mmol (117 mg) of 277 is first deprived of protection with HCl and then reacted with phenylhydrazine for indolization. 0299 Yield after evaporation and preparative HPLC: 15 mg of 276. 0300 ES-MS: 418 (MH) 0301 25 mg of 6,8-dichloro-2,3,4,9-tetrahydro-N-(1S)-1-(hydroxymethyl)-2-methylpropyl-3-(3-phenylpropyl)-1H-carbazole-3-carboxamide 278 is produced analogously with use of 2,4-dichlorophenylhydrazine. 0302 ES-MS: 486 (MH)

Example 38 0303 2,3,4,9-Tetrahydro-3-(3-phenylpropyl)-N-(2-pyridinylmethyl)-1H-carbazole-3-methanamine 279 0304 54 ml of a 1 M solution of LiAlH4 in dry THF is carefully added to a solution of 18 mmol (6 g) of 270 in 250 ml of dry THF under argon at room temperature. After 3 hours of refluxing, it is carefully hydrolyzed with 300 ml of saturated NH4Cl solution and mixed with 250 ml of ether. The aluminum salts are filtered off and washed with ether. Drying the ether phase with Na2SO4 and evaporation of the solvent yield 3.4 g of 8-(3-phenylpropyl)-1,4-dioxaspiro4,5decane-8-methanol 280. 0305 5.86 mmol (1.7 g) of 280 is dissolved in 60 ml of dry DCM and 20 ml of dry DMSO. First 44 mmol (6.1 ml) of TEA and then 17.6 mmol (2.8 g) of SO3-pyridine complex are carefully added at room temperature under nitrogen and stirred for one hour. Then, it is mixed with 200 ml of saturated NH4Cl solution and extracted with 150 ml of ether. Drying the ether phase with Na2SO4 and evaporation of the solvent yield 1.9 g of 8-(3-phenylpropyl)-1,4-dioxaspiro4,5decane-8-carbaldehyde 281 as a colorless oil. 0306 0.719 mmol of sodium triacetoxy borohydride is added to a mixture of 0.359 mmol (103 mg) of 281 and 0.359 mmol (37 ml) of 2-pyridinemethanamine in 2.5 ml of 1,2-dichloroethane. The mixture is stirred under N2 for 3 hours at room temperature. It is mixed with saturated NaHCO3 solution and extracted with ether. The dried and evaporated ether extract yields 101 mg (76%) of white solid N-8(3-phenylpropyl)-1,4-dioxaspiro4,5dec-8-yl-2-pyridinemethanamine 282. 0307 Then, 101 mg of 282 is first removed from protection with HCl as described for 270 and 271 and then reacted with phenylhydrazine for indolization. 0308 Yield after evaporation and preparative HPLC: 71 mg of 279. 0309 ES-MS: 410 (MH) 0310 54 mg of 6,8-dichloro-2,3,4,9-tetrahydro-3-(3-phenylpropyl)-N-(2-pyridinylmethyl)-1H-carbazole-3-methanamine 283 is produced analogously with use of 2,4-dichlorophenylhydrazine. 0311 ES-MS: 478 (MH)

Example 39 0312 (2S)-3-Methyl-2-2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazol-3-ylmethyl-amino-1-butanol 284 0313 0.368 mmol (106 mg) of 281 and 0.368 mmol (38 mg) of valinol are dissolved in 1.5 ml of dry methanol and stirred for 30 minutes at room temperature. After cooling to OC, 0.557 mmol (21 mg) of NaBH4 is added, and it is stirred for 1 hour at room temperature. 0.437 mmol (25 l) of acetic acid is added, and it is stirred at pH 6 for another 2 hours. It is mixed with saturated NaHCO3 solution and extracted with ether. Drying the organic phase with Na2SO4 and evaporation yield 106 mg (77%) of a colorless oil for 270 and 271. 0314 Then, protection is removed as described for 270 and 271, and indolization is done. Yield after evaporation and preparative HPLC: 18 mg of white solid 284. 0315 ES-MS: 405 (MH) 0316 17 mg of (2S)-2-6,8-dichloro-2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazol-3-ylmethylamino-3-methyl-1-butanol 286 is produced analogously with use of 2,4-dichlorophenylhydrazine. 0317 ES-MS: 473 (MH)

Example 40 0318 2,3,4,9-Tetrahydro-3-(3-phenylpropyl)-O-(4-pyridinylmethyl)-1H-carbazole-3-methanol 287 0319 0.689 mmol of NaH (as 55% suspension in mineral oil) is added to a solution of 0.344 mmol (100 mg) of 280 in 10 ml of dry DMF at 0 C. under N2 atmosphere. It is allowed to reach room temperature and stirred for 30 more minutes. 1.377 mmol of 4-(chloromethyl)pyridine is added, and it is stirred overnight at 95-100 C. After cooling to room temperature, it is hydrolyzed with 2 ml of water and extracted with ether. Drying of the LM and evaporation yield 115 mg of yellow oil 288. 0320 Then, protection is removed as described for 270 and 271, and indolization is done. 0321 Yield after evaporation and preparative HPLC: 14 mg of white solid 287. 0322 ES-MS: 411 (MH)

Example 41 0323 Ethyl 3-2,3,4,9-tetrahydro-3-(3-phenylpropyl)-1H-carbazol-3-yl-2-propenoate 289 0324 0.347 mmol of 281 in 0.5 ml of THF is added in drops while being cooled with ice to a solution of 0.378 mmol of ethyl(triphenylphosphoranylidene)acetate in 1 ml of absolute THF. After the addition is completed, it is allowed to heat to room temperature and stirred for another 2 days. Then, it is hydrolyzed with water and extracted with ether. It is dried with Na2SO4, phosphane oxide and dessicant are filtered off, and solvent is removed. 0325 Yield: 80% ethyl 3-8-(3-phenylpropyl)-1,4-dioxaspiro4,5dec-8-yl-2-propenoate 290. 0326 Then, protection is removed as described for 270 and 271, and indolization is done. 0327 Yield after evaporation and preparative HPLC: 9 mg of white solid 289. 0328 ES-MS: 388 (MH) 0329 In addition, compounds nos. 293 to 300, 302 as well as 304 to 306 according to the invention that fall under general formula (I) are obtained according to instructions A, F, G, F, G and O, compound 301 is obtained according to instructions B, F, G, F, G and O, and compound 303 is obtained according to instructions A, F, G, F, G, F, L and O on a 0.2 mmol scale. 35Compound NameNumberMFndMCldPhenylmethyl (1S,2S)-1-(3R)-293612611.68613-(1S)-1-(aminocarbonyl)-2-methylpropylaminocarbonyl-6,8-difluoro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-294620619.75853-(1S,2S)-1-(aminocarbonyl)-2-methylbutylaminocarbonyl-8-methoxy-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-295659658.62293-(1S,2S)-1-(aminocarbonyl)-2-methylbutylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-296659658.62293-(1S)-1-(aminocarbonyl)-3-methylbutylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-297699698.68753-(1S)-1-(aminocarbonyl)-2-cyclohexylethylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-298659658.62293-(1S)-1-(aminocarbonyl)-2,2-dimethylpropylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-299707706.66693-(1S)-1-(aminocarbonyl)-3-phenylpropylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-300685684.66073-(1S)-1(aminocarbonyl)-2-methylbutylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-2-cyclohexylmethyl-carbamatePhenylmethyl (1S,2S)-1-(3R)-301660659.6073-(1S,2S)-1-(carboxy)-2-methylbutylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-2-methylbutylcarbamatePhenylmethyl (1S)-1-(3R)-3-302709708.6391(1S,2S)-1-(aminocarbonyl)-2-methylbutylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-2-(4-hydroxyphenyl)-ethylcarbamatePhenylmethyl (1S)-1-(3R)-3-303723722.6659(1S,2S)-1-(aminocarbonyl)-2-methylbutylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-3-(4-hydroxyphenyl)-propylcarbamatePhenylmethyl (1S)-1-(3R)-3-304707706.6669(1S,2S)-1-(aminocarbonyl)-2-methylbutylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-3-phenylpropylcarbamatePhenylmethyl (1S)-1-(3R)-3-305659658.6229(1S,2S)-1-(aminocarbonyl)-2-methylbutylaminocarbonyl-6,8-dichloro-2-3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-3-methylbutylcarbamatePhenylmethyl (1S)-1-(3R)-3-306659658.6229(1S)-1-(aminocarbonyl)-3-methylbutylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocar-bonyl-3-methylbutylcarbamate

0330 III. Detection of the GnRH-Antagonistic Action of Compounds (I) According to the Invention 0331 Materials: 0332 Buserelin is ordered from Welding (Frankfurt/Main, Germany). The compound is labeled with 125I by use of the chloramine T-method and Na125I (4000 Ci/mmol; Amersham-Buchler, Brunswick, Germany). The labeled substance is purified by reverse phase HPLC on a Spherisorb ODS II column (2504 mm, particle size 3 m) by elution with 50% acetonitrile/0.15% trifluoroacetic acid at a flow rate of 0.5 ml/minute. The specific activity is 2000 Ci/mmol. 0333 All other chemicals are ordered from commercial sources at the highest available purity. 0334 Cell Culture: 0335 Alpha T3-1 cells (Bilezikjian et al., Mol. Endocrinol 5 (1991), 347-355) are cultivated in DMEM medium (Gibco-BRL, Eggenstein-Leopoldshafen, Germany) with penicillin (100 I.U./ml), streptomycin (0.1 mg/ml) and glutamine (0.01 mol/l) and 10% fetal calf serum (FCS; PAA Laboratories, Coelbe, Germany) on plastic tissue culture plates (Nunc, 24524520 mm). CHO-3 cells (Schmid et al., J. Biol. Chem. 275 (2000), 9193-9200) are cultivated under identical conditions, apart from the fact that Ham's F12 medium (Gibco-BRL) is used. 0336 Ten confluent cell culture plates are flushed twice with 50 ml of phosphate-buffered salt solution (PBS). The cells are harvested by scraping them off with a rubber scraper in 5 ml of PBS and sedimented by centrifuging in a laboratory centrifuge (Heraeus) at 800 rpm for 10 minutes. The cell pellet is resuspended in 5 ml of 0.25 mol/l of saccharose/0.01 mol/l of triethanolamine, pH 7.4. The cells are lysed by three cycles of freezing in dry ice/ethanol bath and thawing at room temperature. The lysate is centrifuged at 900 rpm for 10 minutes, and the sediment is discarded. The supernatant is centrifuged at 18,000 rpm in a Sorvall SS34 rotor for 30 minutes. The pellet (cell membranes) is suspended by Potters in 5 ml of assay buffer (0.25 mol/l of saccharose, 0.01 mol/l of triethanolamine, pH 7.5, 1 mg/ml of ovalbumin) and stored in 200 l of aliquots at 20 C. The determination of protein is carried out according to the Bradford method (Anal. Biochem. 72 (1976), 248-254). 0337 Receptor Assay: 0338 Binding studies for competition curves are performed as triplicates. A test sample contains 60 l of cell membrane suspension (10 g of protein for T3-1 cells or 40 g of protein for CHO3 cells), 20 l of 125I-labeled buserelin (100,000 Ipm per sample for competition curves and between 1,500 and 200,000 Ipm for saturation experiments) and 20 l of test buffer or test compound solution. The test compounds are dissolved in distilled water or 50% ethanol. Serial dilutions (5106 mol/l to 5102 mol/l) are produced in test buffer. The unspecific binding is determined in the presence of excess unlabeled buserelin (106 mol/1). The test samples are incubated for 30 minutes at room temperature. Bonded and free ligands are separated by filtration (Whatman GF/C-filter, 2.5 cm diameter) with use of an Amicon 10 collecting device and washed twice with 5 ml of 0.02 mol/l of Tris/HCl, pH 7.4. The filters are moistened with 0.3% polyethylenimine (Serva; Heidelberg, Germany) for 30 minutes to reduce the unspecific binding. The radioactivity that was held up by the filter is determined in a 5-channel gamma-counter (Wallac-LKB 1470 Wizard). 0339 In the table below, the IC50 values that are obtained for the preferred compounds, as defined above, are indicated. 36hGnRH-ExampleReceptor IC50Ca2 ReleaseCompound NameNo.MHuman IC50 MN-(3R)-2,3,4,9-Tetrahydro-3-(1-oxo-2,3-180.00000090.000005diphenylpropyl)amino-1H-carbazol-3 -ylcarbonyl-L-valyl-L-aspartamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-164b0.0000060.0000065methylpropyl-2,3,4,9-tetrahydro-3-(1H-indol-3-ylacetyl)amino-1H-carbazole-3-carboxamide(3S)-N-(1S)-1-(Aminocarbonyl)-2-161b0.00000370.0000036methylpropyl-2,3,4,9-tetrahydro-3-(2-naphthalenylacetyl)amino-1H-carbazole-3 -carboxamideN-(3R)-2,3,4,9-Tetrahydro-3-(2S,3S)-3-220.0000020.000001methyl-1-oxo-2-(1-oxo-3-phenylpropyl)-aminopentylamino-1H-carbazol-3-ylcarbonyl-L-valyl-L-aspartamidePhenylmethyl (1S,2S)-1-(3R)-3-(1S,2S)-640.00000170.00000151-(aminocarbonyl)-2-methylbutylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-450.00000030.0000014-(aminocarbonyl)phenylaminocarbonyl-2-methylpropylaminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-2-methyl-1-(3R)-222a0.00000250.0000032,3,4,9-tetrahydro-3-(1S)-2-methyl-1-(methylamino)carbonylpropylaminocar-onyl-1H-carbazol-3-ylaminocarbonyl-butyl-carbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-580.00000030.00000037(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(2S)-2-181a0.00000070.000003(aminocarbonyl)-1-pyrrolidinylcarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(2S)-2-190a0.0000020.0000005(aminocarbonyl)octahydro-1H-indol-1-ylcarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate2,3,4,9-Tetrahydro-3-(3 -phenylpropyl)-N-(2-2790.0000020.000003pyridinylmethyl)-1H-carbazole-3-methanamine(2S)-3-Methyl-2-2,3,4,9-tetrahydro-3-(3-2840.0000070.000007phenylpropyl)-1H-carbazol-3-ylmethyl-amino-1-butanolN-(1S)-1-(Aminocarbonyl)-2-methylpropyl-1750.0000080.00000182,3,4,9-tetrahydro-3-(4-methoxyphenyl)-acetylamino-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-960.0000040.000003methylpropyl-3-(3 -bromophenyl)acetyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-910.00000240.000002methylpropyl-3-(4-fluorophenyl)acetyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-167a0.0000010.0000026methylpropyl-3-(4-chlorophenyl)acetyl-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide(3R)-N-(1S)-1-(Aminocarbonyl)-2-234a0.0000090.000001methylpropyl-2,3,4,9-tetrahydro-3-(6-phenylhexyl)amino-1H-carbazole-3-carboxamidePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-150a0.000000110.00000028(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-8-methyl-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-148a0.000000080.00000014(aminocarbonyl)-2-methylpropylamino-carbonyl-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-147a0.0000000760.00000025(aminocarbonyl)-2-methylpropylamino-carbonyl-2,3,4,9-tetrahydro-8-methoxy-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-184a0.0000000150.000000045(aminocarbonyl)-2-methylpropylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-267a0.00000040.0000005(hydroxymethyl)-2-methylpropyl-aminocarbonyl-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamate(2S)-1-(3R)-3-(4-Chlorophenyl)acetyl-189a0.00000070.0000005amino-2,3,4,9-tetrahydro-8-methoxy-1H-carbazol-3-ylcarbonyl-2-pyrrolidinecarboxamide6,8-Dichloro-2,3,4,9-tetrahydro-3-(3 -2830.0000010.000003phenylpropyl)-N-(2-pyridinylmethyl)-1H-carbazole-3-methanamine

0340 The compounds of numbers 293 to 306 are tested according to the methods that are indicated below: 0341 Receptor Binding Assay 0342 Materials: 0343 125I-Triptorelin 125I-(D)-Trp6-GnRH is ordered from the Biotrend Company (Cologne, Germany). The specific activity in each case is 2.13 Ci/mmol. All other chemicals are ordered from commercial sources at the highest available purity. 0344 Cell Culture: 0345 Transfixed LTK cells (ATCC No. CCL-11.3) are cultivated in DMEM medium (Invitrogen Life Technologies, Germany) with penicillin (100 I.U./ml), streptomycin (0.1 mg/ml) and glutamine (0.01 mol/l) and 10% fetal calf serum (FCS; Invitrogen Life Technologies, Germany) on plastic tissue culture plates (Nunc, Germany, 24524520 nun). 0346 Testing: 0347 80% confluent cell culture plates are washed twice with 50 ml of phosphate-buffered salt solution (PBS) and dissolved below with 0.01 M EDTA solution. The cells are pelletized by centrifuging at 200g for 5 minutes in a laboratory centrifuge (Kendro, Germany). The cell pellet is resuspended in 3 ml of binding medium (DMEM; 10 mmol of Hepes; 0.5% BSA; 0.1% NaN3; 1 g/l of bacitracin (freshly added, stock 100); 0.1 g/l of SBTI (freshly added, stock 1000), and the cell count is determined by means of trypan blue staining in a Neubauer counting chamber. The cell suspension is set with binding medium to a concentration of 5105 Z/0.05 ml. 0348 Binding tests for competition curves are performed as duplicates. The test substances are used as 10 mmol DMSO solutions. They are diluted with binding medium to 4 the final concentration used. 25 l of the substance dilution is mixed with 25 l of tracer solution (125I-triptorelin). The concentration of tracer is set to about 50,000 cpm (measured in Cobra II, -counter, PE Liefe Science, Germany) in the final reaction volume of 100 l. 0349 200 l of a silicone/paraffin oil mixture (84%:16%) is introduced into 650 l pointed-bottom tubes (Roth, Germany). 50 l of the cell suspension is pipetted thereto and subsequently 50 l of the test substance/tracer mixture. The tubes are sealed and incubated for 60 minutes at 37 C. in an incubator that rotates via the top. After incubation, the samples are centrifuged in a centrifuge (Kendro, Germany) at 900 rpm and subsequently flash-frozen in liquid N2. The tip with the cell pellet is cut off and inserted into the prepared counting tube (Roth, Germany). The remainder of the pointed-bottom tube with the remaining supernatant is also inserted into a counting tube. The measurement is made in a 7-counter for 1 minute/sample. 0350 The evaluation of the samples is carried out after calculating the specific bond in comparison to untreated cells, after the unspecific bond (excess unlabeled ligand, 1 mmol) is removed by means of GraphPad Prism (GraphPad Software Inc., USA). 0351 Functional Reporter Gene Assay 0352 Materials: 0353 All chemicals are ordered from commercial sources at the highest available purity. 0354 Cell Culture: 0355 For performing functional tests, stable, transfixed LTK cells carrying GnRH receptors (ATCC No. CCL-1.3) with a heterologous expression of cAMP responsible elements as well as a CMV minimal promoter-driven luciferase reporter gene are used. 0356 The cells are cultivated in DMEM medium (Invitrogen Life Technologies, Germany) with penicillin (100 I.U./ml), streptomycin (0.1 mg/ml) and glutamine (0.01 mol/l) and 10% fetal calf serum (FCS; Invitrogen Life Technologies, Germany) on plastic tissue culture plates (Nunc, Germany, 24524520 mm). 0357 Testing: 0358 80% confluent cell culture plates are washed twice with 50 ml of phosphate-buffered salt solution (PBS) and subsequently dissolved with trypsin EDTA solution (Invitrogen Life Technologies, Germany). The cells are pelletized by centrifuging at 200g for 5 minutes in a laboratory centrifuge (Kendro, Germany). The cell pellet is resuspended in 3 ml of assay medium (Invitrogen Life Technologies, Germany) with penicillin (100 I.U./ml), streptomycin (0.1 mg/ml) and glutamine (0.01 mol/l) and 10% fetal calf serum (FCS; Invitrogen Life Technologies, Germany), and the cell count is determined by means of trypan blue staining in a Neubauer counting chamber. The cell suspension is set with assay medium to a concentration of 1104 Z/100 l. The cells are suspended on white 96-well microtiter plates (Costar, Germany) and incubated for 18 hours in an incubator. 0359 To perform tests, test substances are diluted as 10 mmol DMSO solutions in assay medium to 6 the final concentration used. 25 l of the test substance is added to 100 l cells and incubated for 60 minutes at 37 C., 5% CO2. Then, the addition of triptorelin (D-Trp6-GnRH)/Rolipram solution (6 mmol/6 mmol) and a renewed incubation are carried out for 6 hours at 37 C., 5% CO2. 0360 After incubation, the addition of 50 l of lysis/detection buffer (LucLite, PE Life Science) and the measurement in a Lumistar luminometer (BMG Labtechnologies GmBH, Germany) are carried out. 0361 The evaluation of the samples is carried out after calculating the inhibition in comparison to untreated stimulated cells, after removal of non-stimulated controls, by means of GraphPad Prism (GraphPad Software, Inc., USA) or alternately by means of OMMM (Accelrys, Germany) Software. 0362 In the table below, EC50-values obtained for compounds 293 to 306 are indicated. 37FunctionalHuman BindingExampleHumanTriptorelinCompound NameNo.EC50 MEC50 MPhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-2930.0000007620.000000332(aminocarbonyl)-2-methylpropylamino-carbonyl-6,8-difiuoro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S,2S)-2940.0000000890.0000000361-(aminocarbonyl)-2-methylbutylamino-carbonyl-8-methoxy-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S,2S)-2950.0000000070.0000000181-(aminocarbonyl)-2-methylbutylamino-carbonyl-6,8-dicloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-2960.0000000140.000000022(aminocarbonyl)-3-methylbutylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-2970.0000002840.000000482(aminocarbonyl)-2-cyclohexylethylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-2980.000000288(aminocarbonyl)-2,2-dimethylpropylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutyl-carbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-2990.0000014970.000001307(aminocarbonyl)-3-phenylpropyl-aminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S)-1-3000.0000000170.000000023(aminocarbonyl)-2-methylbutylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-cyclohexyl-methylcarbamatePhenylmethyl (1S,2S)-1-(3R)-3-(1S,2S)-3010.0000001760.0000005381-(carboxy)-2-methylbutylaminocarbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-methylbutylcarbamatePhenylmethyl (1S)-1-(3R)-3-(1S,2S)-1-3020.0000003240.000000475(aminocarbonyl)-2-methylbutylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-2-(4-hydroxyphenyl)ethylcarbamatePhenylmethyl (1S)-1-((3R)-3-(1S,2S)-1-3030.000000021(aminocarbonyl)-2-methylbutylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-3-(4-hydroxyphenyl)propylcarbamatePhenylmethyl (1S)-1-(3R)-3-(1S,2S)-1-3040.0000000180.000000038(aminocarbonyl)-2-methylbutylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-3-phenylpropylcarbamatePhenylmethyl (1S)-1-(3R)-3-(1S,2S)-1-3050.000000056(aminocarbonyl)-2-methylbutylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-3-methylbutylcarbamatePhenylmethyl (1S)-1-(3R)-3-(1S)-1-3060.000000077(aminocarbonyl)-3-methylbutylamino-carbonyl-6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylaminocarbonyl-3-methylbutylcarbamate

0363 The entire disclosures of all applications, patents and publications, cited herein and of corresponding German Application No. 101 64 564.3, filed Dec. 14, 2001, and U.S. Provisional Application Serial No. 60/341,878, filed Dec. 21, 2001, are incorporated by reference herein. 0364 The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples. 0365 From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention and, without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.

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