RU2007105561A - DERIVATIVES OF TETRAHYDROCARBAZOLES AND PHARMACEUTICAL COMPOSITION ON THEIR BASIS - Google Patents

Claims (37)

1. Derivatives of tetrahydrocarbazole, characterized in that they are represented by the following structural formula (formula I)

in which X ₁ means S, O or S ⁺ -O ^- , X ₂ and X ₃ independently of one another mean O or geminally attached H ₂ , R1 and R2 are independently selected from the group consisting of a hydrogen atom, aryl, alkyl and arylalkyl radicals, which are optionally substituted in the alkyl and / or aryl group with up to 3 substituents independently selected from the group consisting of atoms halogen, —CN and —O-alkyl groups, where R1 and R2 are both, in particular hydrogen atoms, R3 is an alkyl, arylalkyl or heteroarylalkyl radical, which are optionally substituted with up to 3 substituents independently selected from the group consisting of halogen atoms, —CN, —CO — O — R12, —CO — NR12R12 ′, —OH groups , -O-R13, -O-CO-R13, -O-SO ₂ , -OR12, -O-SO ₂ -R12, -SO ₂ -OR12, -SO-R12, -O-PO (OR12) (OR12 '), -O-PO (NR12R12') ₂ , -O-CO-O-R13, -O-CO-NR12R12 ', -O-CS-NR12R12', -S-R12, -NR12R12 ', -NH- CO-R13, -NH-SO ₂ -R12, -NH-CO-O-R13, -NH-CO-NHR12, -NH-C (NH) -NH ₂ , R4, R5, R6 and R7 are independently selected from the group consisting of a hydrogen atom, halogen atoms, —CN, —CONH ₂ , —COOH, —CF ₃ , —O-alkyl, —OCF ₃ , —NO2, and alkyl, arylalkyl and heteroarylalkyl radicals; R9 is a hydrogen atom, an alkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl radical, preferably a hydrogen atom; R10 is a hydrogen atom or a radical —R11, —CO — R11, —CO — OR11, —CO — NHR11, —C (NH) —NHR11, —SO ₂ —R11, or —SO ₂ —NHR-11; R11 is an alkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl radical, which are optionally substituted with one or more substituents independently selected from the group consisting of halogen atoms, —CN, alkyl, —CF ₃ , —OCF ₃ , -OH, -O-alkyl and -O- (CH ₂ CH ₂ -O) _n -CH ₃ ; R8 is —C ₁ -C ₆ alkylaryl or —C ₁ -C ₆ alkylheteroaryl, wherein the aryl or heteroaryl group is substituted with one to three substituents, preferably one independently selected from the group consisting of —O— (CH ₂ CH ₂ —O) _n —CH ₃ , —O — CO — R12, —O — CO— (CH ₂ CH ₂ —O) _n —CH ₃ , —O — SO ₂ —OR12, —O — SO ₂ - R12, -O-PO (OR12) (OR12 '), -O-PO (NR12R12') ₂ , -O-CO-OR13, -O-CO-NR12R12 'and -O-CS-NR12R12' or, if at least, (i) X ₁ means S, or (ii) R10 is not a hydrogen atom, and R11 is an arylalkyl or heteroarylalkyl radical which are substituted on the aryl or heteroaryl group by one or more substituents independently selected from the group consisting of halogen atoms, —CN, —alkyl, —CF groups ₃ , -OCF ₃ , -OH, -O-alkyl and -O- (CH ₂ CH ₂ -O) _n -CH ₃ , R8 also takes the values indicated for R3; R12 and R12 'independently of one another represent a hydrogen atom or an alkyl, arylalkyl, aryl, heteroarylalkyl or heteroaryl radical, preferably hydrogen, R13 is selected from alkyl, arylalkyl, aryl, heteroarylalkyl or heteroaryl radicals or the group - (CH ₂ CH ₂ —O) _n —CH ₃ and n is any integer from 1 to 10, preferably from 1 to 6; and physiologically tolerated salts, derivatives or analogs of a compound of general formula (I), wherein salts can be prepared by neutralizing the bases with inorganic or organic acids or by neutralizing the acids with inorganic or organic bases, where the compound of general formula (I) and its salts, derivatives or analogues can exist in the form of their racemates, in the form of pure enantiomers and / or diastereomers, or in the form of a mixture of such enantiomers and / or diastereomers, in the form of tautomers, their solvates and hydrates and their polymorphic forms. 2. Derivatives according to claim 1, in which the compound of formula (I) has an R configuration on a carbon atom substituted by —NH — CX ₃ and —CX ₂ —NH— radicals. 3. The derivatives of claim 2, wherein the compound of formula (I) has an S configuration on a carbon atom substituted with —CX ₃ —NH—, —R8 and —NR9R10 radicals, and also an S configuration on a carbon atom substituted with —NH— radicals CX ₂ -, -R3 and -CX ₁ -NR1R2. 4. Derivatives according to any one of claims 1 to 3, in which X is S, and R8 is an alkyl, arylalkyl or heteroarylalkyl radical, which are optionally substituted with up to 3 substituents independently selected from the group consisting of halogen atoms, - CN, -CO-O-R12, -CO-NR12R12 ', -OH, -O-R13, -O-CO-R13, -O-SO ₂ -OR12, -O-SO ₂ -R12, -SO ₂ - OR12, -SO-R12, -O-PO (OR12) (OR12 '), -O-PO (NR12R12') ₂ , -O-СО-O-R13, -O-CO-NR12R12 ', -O-CS -NR12R12 ', -S-R12, -NR12R12', -NH-CO-R13, -NH-SO ₂ -R12, -NH-CO-O-R13, -NH-CO-NHR12, -NH-C (NH ) -NH ₂ . 5. The derivatives of claim 1, wherein R8 is an alkyl, arylalkyl or heteroarylalkyl radical, which is optionally substituted with up to 3 substituents independently selected from the group consisting of halogen atoms, —CN, —CO — OR12, —CO— groups NR12R12 ', -OH, -O-R13, -O-CO-R13, -O-SO ₂ -OR12, -O-SO ₂ -R12, -SO ₂ -OR12, -SO-R12, -O-PO ( OR12) (OR12 '), -O-PO (NR12R12') ₂ , -O-CO-OR13, -O-CO-NR12R12 ', -O-CS-NR12R12', -S-R12, -NR12R12 ', - NH-CO-R13, -NH-SO ₂ -R12, -NH-CO-O-R13, -NH-CO-NHR12, -NH-C (NH) -NH ₂ . 6. Derivatives according to any one of claims 1 to 3, in which R10 represents the radical —R11, —CO — R11, —CO — OR11, —CO — NHR11, —C (NH) —NHR11, —SO ₂ —R11, or —SO ₂ NHR11, R11 is an arylalkyl or heteroarylalkyl radical which is substituted on the aryl or heteroaryl group by one or more substituents independently selected from the group consisting of halogen atoms, —CN, alkyl, —CF ₃ , —OCF ₃ , —OH, —O— alkyl and —O— (CH ₂ CH ₂ —O) _n —CH ₃ ; and R8 is an alkyl, arylalkyl or heteroarylalkyl radical which is optionally substituted with up to 3 substituents independently selected from the group consisting of halogen atoms, —CN, —CO — O — R12, —CO — NR12R12 ′, —OH, —O groups -R13, -O-CO-R13, -O-SO ₂ -OR12, -SO ₂ -OR12, -O-SO ₂ -R12, -SO-R12, -O-PO (OR12) (OR12 '), - O-PO (NR12R12 ') ₂ , -O-CO-O-R13, -O-CO-NR12R12', -O-CS-NR12R12 ', -S-R12, -NR12R12', -NH-CO-R13, -NH-SO ₂ -R12, -NH-CO-O-R13, -NH-CO-NHR12, -NH-C (NH) NH ₂ . 7. Derivatives according to any one of claims 1 to 3, in which R8 represents either a -C ₁ -C ₆ -alkylaryl or -C ₁ -C ₆ -alkylheteroaryl radical, where the aryl or heteroaryl group is substituted with one to one substituents three, preferably one, independently selected from the group consisting of —O— (CH ₂ CH ₂ —O) _n —CH ₃ , —O — CO— (CH ₂ CH ₂ —O—) _n —CH ₃ , —O -SO ₂ OR12, -O-SO ₂ R12, -O-PO (OR12) (OR12 '), -O-PO (NR12R12') ₂ , -O-CO-OR13, -O-CONR12R12 'and -O- CS-NR12R12 '. 8. Derivatives according to any one of claims 1 to 3, in which at least one, preferably at least two, of the radicals R4, R5, R6, and R7, preferably R5 and R7, are not a hydrogen atom. 9. The derivatives of claim 8, in which the radicals R4 and R6 are both hydrogen atoms and the radicals R5 and R7 are independently selected from the group consisting of hydrogen atoms, halogens, —CN, —CF ₃ , —O-alkyl groups and —OCF ₃ , and are preferably hydrogen, halogen atoms or a —CF ₃ group. 10. The derivatives of claim 9, wherein R5 is a hydrogen or halogen atom and R7 is a halogen atom or —CF ₃ . 11. Derivatives according to any one of claims 1 to 3, in which X ₂ and X ₃ are both O. 12. Derivatives according to any one of claims 1 to 3, in which R3 is a C ₁ -C ₆ alkyl radical, preferably a C ₁ -C ₄ alkyl radical. 13. Derivatives according to any one of claims 1 to 3, in which R1 and R2 are both hydrogen atoms. 14. Derivatives according to any one of claims 1 to 3, in which R9 and, if any, R12 and R12 'are all hydrogen atoms. 15. Derivatives according to any one of claims 1 to 3, in which R13 represents a phenyl-C ₁ -C ₄ -alkyl radical or a group - (CH ₂ CH ₂ -O) _n -CH ₃ . 16. Derivatives according to any one of claims 1 to 3, in which R10 represents a radical -CO-R11 or -CO-OR11 or a radical R11. 17. Derivatives according to any one of claims 1 to 3, in which R11 is a phenyl-C ₁ -C ₄ -alkyl radical, preferably a benzyl or phenylethyl radical, which is optionally substituted in the phenyl group with substituents in an amount of from 1 to 3, preferably one or two independently selected from the group consisting of halogen atoms, groups —C ₁ -C ₄ -alkyl, —CF ₃ , —OCF ₃ , —OH, —O — C ₁ -C ₄ -alkyl and —O- (CH ₂ CH ₂ -O) _n CH ₃ . 18. Derivatives according to any one of claims 1 to 3, in which X ₁ represents O, S or S ⁺ -O ^- , X ₂ and X ₃ both represent O, R1 and R2 both represent a hydrogen atom, R3 is a C ₁ -C ₆ alkyl radical, preferably a C ₁ -C ₄ alkyl radical, R4 and R6 both represent a hydrogen atom, R5 represents a hydrogen atom or a halogen atom, R7 represents a halogen atom or a —CF ₃ group, R9 represents a hydrogen atom, R10 represents a radical —CO — R11 or —CO — OR11 or a radical R11, R11 represents a phenyl-C ₁ -C ₄ -alkyl radical, preferably a benzyl or phenylethyl radical, which is optionally substituted in the phenyl group by substituents in an amount of one to three, preferably one or two, independently selected from the group consisting of halogen atoms, groups -C ₁ -C ₄ -alkyl, -CF ₃ , -OCF ₃ , -OH, -O-C ₁ -C ₄ -alkyl and -O- (CH ₂ CH ₂ -O) _n -CH ₃ -, and R8 represents a phenyl-C ₁ -C ₄ -alkyl radical, preferably a benzyl or phenylethyl radical, which is substituted on the phenyl group by a substituent selected from the group consisting of -O- (CH ₂ CH ₂ -O) _n -CH ₃ groups, —O — CO— (CH ₂ CH ₂ —O—) _n —CH ₃ , and —O — PO (OR12) (OR12 ′), —O — CO — OR13, or, if at least (i) X ₁ represents S, or (ii) R11 represents a phenyl-C ₁ -C ₄ alkyl radical, preferably a benzyl or phenylethyl radical, which is substituted in the phenyl group by at least one of the substituents independently selected from the group consisting of halogen atoms, the groups-C ₁ - C ₄ -alkyl, -CF ₃ , -OCF ₃ , -OH, -O-C ₁ -C ₄ -alkyl and -O- (CH ₂ CH ₂ -O) _n -CH ₃ , R8 also represents a C ₁ -C ₆ alkyl radical, preferably a C ₁ -C ₄ alkyl radical, or a phenyl C ₁ -C ₄ alkyl radical, preferably a benzyl or phenylethyl radical, the radicals being optionally substituted with a substituent selected from the group consisting of the groups —OH, —O — R13 and —NR12R12 ′; R12, R12 'independently from each other are a hydrogen atom or a C ₁ -C ₄ -alkyl, benzyl or phenylethyl radical, preferably a hydrogen atom; R13 is selected from C ₁ -C ₄ -alkyl, phenyl-C ₁ -C ₄ -alkyl and phenyl radicals or is a group - (CH ₂ CH ₂ -O) _n -CH ₃ , and is preferably a benzyl or phenylethyl radical, and n is any integer from 1 to 6, preferably 4. 19. The derivatives of claim 18, wherein X ₁ represents S or S ⁺ -O ^- , preferably S, R3 and R8 are both C ₁ -C ₄ alkyl radicals, R4 and R6 are both hydrogen atoms, R5 and R7 are both halogen atoms, or R5 is a hydrogen atom and R7 is a —CF ₃ group, R10 is a radical -CO-R11, R11 represents a benzyl or phenylethyl radical substituted in the phenyl group by one or two substituents independently selected from the group consisting of halogen atoms, —OCF ₃ and —OCH ₃ groups. 20. The derivatives of claim 18, wherein X ₁ represents O, R3 is a C ₁ -C ₄ alkyl radical, R4 and R6 are both hydrogen atoms, R5 and R7 are both halogen atoms, or R5 is a hydrogen atom and R7 is a —CF ₃ group, R10 is the radical —CO — R11 or —CO — OR 11 or the radical R11, R11 represents a benzyl or phenylethyl radical substituted in the phenyl group by one or two halogen atoms, and R8 represents a C ₁ -C ₄ alkyl, benzyl or phenylethyl radical, wherein the phenyl radical is optionally substituted with an —OH group. 21. The derivatives of claim 18, wherein X ₁ is S or S ⁺ -O ^- , preferably S, R3 is a C ₁ -C ₄ alkyl radical, R4 and R6 are both hydrogen atoms, R5 and R7 are both halogen atoms, R10 is a radical -CO-OR11, R11 represents a benzyl or phenylethyl radical substituted in the phenyl group, if necessary, with one or two halogen atoms, and R8 represents a C ₁ -C ₄ alkyl, benzyl or phenylethyl radical, wherein the phenyl radical is optionally substituted with an —OH group. 22. The derivatives of claim 18, wherein X ₁ is O, S or S ⁺ -O ^- , preferably O or S, R3 is a C ₁ -C ₄ alkyl radical, R4 and R6 are both hydrogen atoms, R5 and R7 are both halogen atoms, or R5 is a hydrogen atom and R7 is a —CF ₃ group, R10 is a radical -CO-R11 or -CO-OR11, R11 represents a benzyl or phenylethyl radical substituted in the phenyl group, if necessary, with one or two halogen atoms, and R8 represents a benzyl or phenylethyl radical in which the phenyl group is substituted by the radical —O — PO (OH) ₂ . 23. The derivatives according to claim 1, selected from the group consisting of the following compounds {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylpropylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylpropyl} -carbamic acid 4-chlorobenzyl ether (1), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylpropylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 4-chlorobenzyl ether (2), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 4-chlorobenzyl ether (3), (R) -6,8-dichloro-3 - {(S) -2- [2- (2-fluorophenyl) acetylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H-carbazole- 3-carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) amide (4), (R) -6,8-dichloro-3 - {(S) -2- [2- (3-fluorophenyl) acetylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H-carbazole- 3-carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) -amide (5), {(S) -1 - [(R) -3 - ((S) -carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbamoyl] -2-methylbutyl} -carbamic acid 2-chlorobenzyl ether (6), {(S) -1 - [(R) -6,8-dichloro-3 - ((S) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} carbamic acid benzyl ester (7), benzyl 4 - {(S) -3-benzyloxycarbonylamino-3 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro -1H-carbazol-3-ylcarbamoyl] propyl} phenyl carbonate (8), [(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2- (4-phosphonooxyphenyl) ethyl] carbamic acid benzyl ester (9), [(S) -1 - [(R) -6,8-dichloro-3 - ((S) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -3- (4-hydroxyphenyl) propyl] carbamic acid benzyl ether (10), [(S) -1 - [(R) -3 - ((S) -carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbamoyl] -3- (4-phosphonooxyphenyl) propyl] carbamic acid benzyl ester (11), [(S) -1 - [(R) -6,8-dichloro-3 - ((8) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -3- (4-phosphonooxyphenyl) propyl] carbamic acid benzyl ester (12), (R) -6,8-dichloro-3 - {(S) -2- [2- (2-fluorophenyl) acetylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H-carbazole- 3-carboxylic acid ((3) -2-methyl-1-thiocarbamoylbutyl) -amide (13), (R) -6,8-dichloro-3 - [(S) -2- [2- (2-fluorophenyl) acetylamino] -4- (4-hydroxyphenyl) butyrylamino] -2,3,4,9-tetrahydro -1H-carbazole-3-carboxylic acid ((S) -2-methyl-1-thiocarbamoylbutyl) amide (14), phosphoric acid mono- (4 - {(S) -3 - [(R) -6,8-dichloro-3 - ((S) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro -1H-carbazol-3-ylcarbamoyl] -3- [2- (2-fluorophenyl) acetylamino] propyl} phenyl ether (15), (R) -6,8-dichloro-3 - {(S) -2- [3- (4-fluorophenyl) propionylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H-carbazole-3 -carboxylic acid ((S) -1-carbamoyl-2-methylpropyl) -amide (16), (S) -5 - [(R) -3 - ((S) -1-carbamoyl-2-methylpropylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazol-3-ylcarbamoyl ] -5- [3- (4-fluorophenyl) propionylamino] pentylammonium trifluoroacetate (17), (S) -6,8-dichloro-3 - {(S) -2- [3- (2-hydroxyphenyl) propionylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H-carbazole- 3-carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) amide (18), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2- [4- (2- {2- [2- (2-methoxy-ethoxy) ethoxy] ethoxy} ethoxy) phenyl] ethyl} carbamic acid benzyl ester (19), (R) -6,8-dichloro-3 - ((S) -2- {3- [2- (2- {2- [2- (2-methoxyethoxy) ethoxy] ethoxy} ethoxy) phenyl ] -propionylamino} -3-methylpentanoylamino) -2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) amide (20), (R) -6,8-dichloro-3 - ((S) -2- (2- [2- (2- {2- [2- (2-methoxyethoxy) ethoxy] ethoxy} ethoxy) phenyl ] -acetylamino} -3-methylpentanoylamino) -2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) amide (21), (R) -6,8-dichloro-3 - [(S) -2- [3- (2-fluorophenyl) propionylamino] -4- (4-hydroxyphenyl) butyrylamino] -2,3,4,9-tetrahydro -1H-carbazole-3-carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) amide (22), (R) -6,8-dichloro-3 - {(S) -2- [3- (2-fluorophenyl) propionylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H-carbazole-3 -carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) -amide (23), {(S) -1 - [(R) -6,8-dichloro-3 - ((S) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -3- [4- (2- {2- [2- (2-methoxyethoxy) ethoxy] ethoxy} ethoxy) phenyl] propyl} carbamic acid benzyl ester (24), {(S) -1 - [(R) -8-chloro-6-fluoro-3 - ((S) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro-1H-carbazole- 3-ylcarbamoyl] -2-methylbutyl} -carbamic acid benzyl ester (25), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 3-methylbenzyl ether (26), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 2,6-difluorobenzyl ether (27), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 3,5-difluorobenzyl ether (28), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 3,5-dichlorobenzyl ether (29), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 3-fluorobenzyl ether (30), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 2-fluorobenzyl ether (31), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 3-chlorobenzyl ether (32), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -8-chloro-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole- 3-ylcarbamoyl] -2-methylbutyl} -carbamic acid 3,5-difluorobenzyl ether (33), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -8-chloro-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole- 3-ylcarbamoyl] -2-methylbutyl} -carbamic acid 3-fluorobenzyl ester (34), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -8-chloro-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole- 3-ylcarbamoyl] -2-methylbutyl} -carbamic acid 2-fluorobenzyl ether (35), [(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -3- (4-hydroxyphenyl) propyl] carbamic acid 3-fluorobenzyl ether (37), [(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -3- (4-hydroxy-phenyl) propyl] -carbamic acid 2-fluorobenzyl ether (38), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 2- (2-fluorophenyl) ethyl ether (40), {(S) -1 - [(R) -8-chloro-6-fluoro-3 - ((S) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro-1H-carbazole- 3-ylcarbamoyl] -2-methylbutyl} -carbamic acid 2-fluorobenzyl ether (41), {(S) -1 - [(R) -8-chloro-6-fluoro-3 - ((S) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro-1H-carbazole- 3-ylcarbamoyl] -2-methylbutyl} -carbamic acid 3-fluorobenzyl ether (42), [(S) -1 - [(R) -6,8-dichloro-3 - ((S) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -3- (4-hydroxyphenyl) propyl] carbamic acid 2-fluorobenzyl ether (43), [(S) -1 - [(R) -6,8-dichloro-3 - ((S) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -3- (4-hydroxyphenyl) propyl] carbamic acid 3-fluorobenzyl ether (45), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 3-methoxybenzyl ether (47), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 4-fluorobenzyl ether (48), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 2-methylbenzyl ether (49), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 2,3-dimethoxybenzyl ether (50), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 2-methoxybenzyl ether (51), (R) -6,8-dichloro-3 - {(S) -2- [2- (2-fluorophenyl) ethylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H-carbazole-3 -carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) amide (52), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 2-trifluoromethylbenzyl ether (53), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 3-trifluoromethylbenzyl ether (54), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 3-trifluoromethoxybenzyl ether (55), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -6,8-dichloro-2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 2-trifluoromethoxybenzyl ether (56), {(S) -1 - [(R) -6,8-dichloro-3 - ((S) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro-1H-carbazole-3- ilcarbamoyl] -2-methylbutyl} -carbamic acid 4-fluorobenzyl ether (57), (R) -6,8-dichloro-3 - {(S) -2- [2- (4-fluorophenyl) ethylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H-carbazole-3 -carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) amide (58), (R) -6,8-dichloro-3 - {(S) -2- [2- (2,6-difluorophenyl) acetylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H- carbazole-3-carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) -amide (59), {(S) -1 - [(R) -8-chloro-6-fluoro-3 - ((S) -2-methyl-1-thiocarbamoylbutylcarbamoyl) -2,3,4,9-tetrahydro-1H-carbazole- 3-ylcarbamoyl] -2-methylbutyl} -carbamic acid 4-fluorobenzyl ether (60), (R) -6,8-dichloro-3 - {(S) -2- [2- (3-fluorophenyl) ethylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H-carbazole- 3-carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) amide (61), (R) -8-chloro-3 - {(S) -2- [2- (2,6-difluorophenyl) acetylamino] -3-methylpentanoylamino} -6-fluoro-2,3,4,9-tetrahydro 1H-carbazole-3-carboxylic acid ((S) -2-methyl-1-thiocarbamoylbutyl) amide (62), (R) -8-chloro-6-fluoro-3 - {(S) -2- [2- (4-fluorophenyl) ethylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H-carbazole -3-carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) -amide (63), {(S) -1 - [(R) -3 - ((S) -1-carbamoyl-2-methylbutylcarbamoyl) -8-chloro-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole- 3-ylcarbamoyl] -2-methylbutyl} -carbamic acid 4-fluorobenzyl ether (64), (R) -8-chloro-6-fluoro-3 - {(S) -2- [2- (4-fluorophenyl) acetylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H- carbazole-3-carboxylic acid ((S) -2-methyl-1-thiocarbamoylbutyl) amide (65), (R) -8-chloro-3 - {(S) -2- [2- (2,4-difluorophenyl) acetylamino] -3-methylpentanoylamino} -6-fluoro-2,3,4,9-tetrahydro- 1H-carbazole-3-carboxylic acid ((S) -2-methyl-1-thiocarbamoylbutyl) amide (66), (R) -8-chloro-6-fluoro-3 - {(S) -2- [2- (4-fluorophenyl) ethylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H -carbazole-3-carboxylic acid ((S) -2-methyl-1-thiocarbamoylbutyl) -amide (67), (R) -8-chloro-6-fluoro-3 - {(S) -2- [2- (2-fluorophenyl) acetylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H- carbazole-3-carboxylic acid ((S) -2-methyl-1-thiocarbamoylbutyl) amide (68), (R) -8-chloro-6-fluoro-3 - {(S) -2- [2- (2-fluorophenyl) acetylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H- carbazole-3-carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) amide (69), (R) -3 - {(S) -2- [2- (2-fluorophenyl) acetylamino] -3-methylpentanoylamino} -8-trifluoromethyl-2,3,4,9-tetrahydro-1H-carbazole-3- carboxylic acid ((S) -2-cyclopropyl-1-thiocarbamoylethyl) -amide (70), (R) -3 - {(S) -2- [2- (2,6-difluorophenyl) acetylamino] -3-methylpentanoylamino} -8-trifluoromethyl-2,3,4,9-tetrahydro-1H-carbazole- 3-carboxylic acid ((S) -2-cyclopropyl-1-thiocarbamoylethyl) -amide (71), (R) -8-chloro-6-fluoro-3 - {(S) -2- [2- (2-fluorophenyl) acetylamino] -3-methylpentanoylamino} -2,3,4,9-tetrahydro-1H- carbazole-3-carboxylic acid ((S) -2-cyclopropyl-1-thiocarbamoylethyl) -amide (72), (R) -3 - {(S) -2- [2- (2,6-difluorophenyl) acetylamino] -3-methylpentanoylamino} -8-trifluoromethyl-2,3,4,9-tetrahydro-1H-carbazole- 3-carboxylic acid ((S) -2-methyl-1-thiocarbamoylbutyl) amide (73), (R) -3 - {(S) -2- [2- (2,6-difluorophenyl) acetylamino] -3-methylpentanoylamino} -8-trifluoromethyl-2,3,4,9-tetrahydro-1H-carbazole- 3-carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) amide (74), (R) -3 - {(S) -2- [2- (2-fluorophenyl) acetylamino] -3-methylpentanoylamino} -8-trifluoromethyl-2,3,4,9-tetrahydro-1H-carbazole-3- carboxylic acid ((S) -1-carbamoyl-2-methylbutyl) amide (75), (R) -3 - {(S) -2- [2- (2-fluorophenyl) acetylamino] -3-methylpentanoylamino} -8-trifluoromethyl-2,3,4,9-tetrahydro-1H-carbazole-3- carboxylic acid ((S) -2-methyl-1H-thiocarbamoylbutyl) -amide (76), (R) -8-chloro-3 - {(S) -2- [2- (2,6-difluorophenyl) acetylamino] -3-methylpentanoylamino} -6-fluoro-2,3,4,9-tetrahydro 1H-carbazole-3-carboxylic acid ((S) -2-cyclopropyl-1-thiocarbamoylethyl) amide (77). 24. Derivatives according to any one of claims 1 to 23, which are drugs. 25. A pharmaceutical composition comprising a pharmacologically active amount of at least one of the derivatives according to claims 1-23. 26. The composition according A.25, in which the active ingredient is contained in a standard dose of from 0.001 to 100 mg per kg of body weight of the patient. 27. The composition according A.25, which further comprises at least one pharmaceutically acceptable carrier. 28. The composition according to any one of paragraphs.25-27, which contains at least one other pharmaceutically active substance. 29. The use of derivatives according to any one of claims 1 to 23 for the preparation of an agent for the treatment or prevention of pathological conditions mediated by a G-protein coupled receptor, or pathological conditions that can be treated by modulating this receptor. 30. The application of clause 29, wherein the G protein conjugated receptor is an LHRH receptor. 31. The application of clause 29, wherein the G-protein coupled receptor is a receptor for the neurokinin family, in particular the NK, and / or the NK ₂ receptor. 32. The application of clause 30, in which the derivatives according to any one of claims 1 to 23 act as antagonists of the LHRH receptor. 33. The application of clause 31, in which the derivatives according to any one of claims 1 to 22 act as antagonists of the NK ₁ and / or NK ₂ receptor. 34. The use according to claim 30 or 32 as a means for treating benign or malignant neoplasms, for controlling male reproductive function, in hormone therapy, in hormone replacement therapy, for treating and / or controlling female reproductive insufficiency or infertility, for controlled stimulation of the ovaries at conception in vitro, for female contraception and for protection against side effects during chemotherapy. 35. The application of claim 30 or 32, wherein the pathological conditions mediated by the LHRH receptor or pathological conditions that can be treated by modulating the LHRH receptor are selected from the group consisting of benign prostatic hyperplasia (BPH), endometriosis, uterine fibroids, uterine fibroids, endometrial hyperplasia, dysmenorrhea, dysfunctional uterine bleeding (menorrhagia, metrorrhagia), early puberty, hirsutism, polycystic ovary syndrome, hormone-dependent neoplastic diseases, HIV infections or AIDS, neurological or neurodegenerative disorders, AIDS-dependent complex (ARC), Kaposi’s sarcoma, brain and / or nervous system tumors and / or meningitis, dementia and Alzheimer's disease. 36. The application of claim 35, wherein the hormone-dependent neoplasms are selected from the group consisting of prostate cancer, breast cancer, uterine cancer, endometrial cancer, cervical cancer, ovarian cancer. 37. The use according to claim 31 or 33 as a means for treating or preventing nausea and vomiting, for treating pain, inflammation, as well as rheumatic and arthritic pathological conditions.