RU2319692C2 - Derivatives of tetrahydrocarbazole, method for preparing tetrahydrocarbazole (variants), their using (variants) and pharmaceutical composition possessing activity of antagonist of gonadotropin-releasing hormone (variants) - Google Patents

Derivatives of tetrahydrocarbazole, method for preparing tetrahydrocarbazole (variants), their using (variants) and pharmaceutical composition possessing activity of antagonist of gonadotropin-releasing hormone (variants) Download PDF

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RU2319692C2
RU2319692C2 RU2004121776/04A RU2004121776A RU2319692C2 RU 2319692 C2 RU2319692 C2 RU 2319692C2 RU 2004121776/04 A RU2004121776/04 A RU 2004121776/04A RU 2004121776 A RU2004121776 A RU 2004121776A RU 2319692 C2 RU2319692 C2 RU 2319692C2
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amino
carbonyl
tetrahydro
methylbutyl
carbazol
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Маркус КОППИЦ (DE)
Маркус КОППИЦ
Ханс Петер МУН (DE)
Ханс Петер Мун
Клаус ПАУЛИНИ (DE)
Клаус ПАУЛИНИ
Хольгер ХЕСС-ШТУМП (DE)
Хольгер Хесс-Штумп
Кен ШОУ (US)
Кен ШОУ
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Центарис Гмбх
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Abstract

FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel derivatives of tetrahydrocarbazole of the general formula (I):
Figure 00000002
wherein R1 means hydrogen atom (H), (C1-C6)-alkyl and can be optionally substituted with groups aryl, heteroaryl or -COOR11 wherein aryl or heteroaryl can be substituted with up to three substitutes that are chosen independently from group comprising -NO2, -CH3, -CF3, -OCH3, -OCF3 and halogen atoms; R11 means H, (C1-C12)-alkyl, (C1-C12)-aralkyl, aryl, heteroaryl, -COCH3 and can be optionally substituted with one substitute chosen from group comprising -CONH2, -COCH3, -COOCH3, -SO2CH3 and aryl; each R2, R3, R4 and R5 means independently H, halogen atom, -COOH, - CONH2, -CF3, -OCF3, -NO2, (C1-C6)-alkyl, (C1-C6)-alkoxy group, (C1-C12)-aralkyl, aryl, heteroaryl; R6 means -CONR8R9, -COOR8, -CH2NR8R9, -CH2R8, -CH2OR8; each R8 and R9 means independently H, (C1-C12)-alkyl, (C1-C12)-aralkyl, (C1-C12)-heteroaryl, aryl or heteroaryl wherein each of them can be with one or more substitutes chosen from group comprising -OH, -NH2, -CONHR10, -COOR10, -NH-C(=NH)-NH2 and halogen atom and wherein R10 means H, (C1-C12)-alkyl, (C1-C12)-aralkyl, aryl or heteroaryl and it is substituted optionally with group -CON(R11)2, or wherein radicals R8 and R9 in common with nitrogen atom to which they are bound form heterocyclic structure; R7 means H, (C1-C12)-alkyl, (C1-C12)-aralkyl, aryl or heteroaryl, -NR12R13, -NHCOR14, -NHCONHR14, -NHCOOR14, -NHSO2R14 and can be substituted optionally with one or more substitutes chosen from group comprising -OH, -NH2, -CONH2, -COOH and halogen atom; each among R12 and R13 means independently H, (C1-C12)-alkyl and can be substituted optionally with one or more substitutes chosen from aryl, heteroaryl that in turn can comprise up to three substitutes chosen independently from -NO2, -CH3, -CF3, -OCH3, -OCF3 and halogen atom; R14 means H, (C1-C12)-alkyl, (C1-C12)-aralkyl, aryl or heteroaryl that can be substituted optionally with one or more substitutes chosen from group comprising -NO2, -CH3, -OR11, -CF3, -OCF3, -OH, -N(R11)2, -OCOR11, -COOH, -CONH2, -NHCONHR11, -NHCOOR11 and halogen atom; each radical among Ra, Rb, Rc, Rd, Re and Rf means independently H, halogen atom, -COOH, -CONH2, -CF3, -OCF3, -NO2, (C1-C6)-alkyl, (C1-C6)-alkoxy group, aryl or heteroaryl wherein heteroaryl and heterocyclic group if it presents means pyridinyl, pyrrolidinyl, indolyl and under condition that compound of the general formula (I) is not chosen from group comprising 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, 3-acetamido-1,2,3,4-tetrahydrocarbazole 3-carboxylic acid methyl ester, 3-acetamido-1,2,3,4-tetrahydrocarbazole 3-carboxylic acid (-)-menthyl ester, 3-tert.-butoxycarbonylamino-1,2,3,4-tetrahydrocarbazole 3-carboxylic acid, 9-methyl-1,2,3,4-tetrahydrocarbazole 4-carboxylic acid, 6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazole 4-carboxylic acid, 9-methyl-1,2,3,4-tetrahydrocarbazole 4-carboxamide, 6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazole 4-carboxamide. Compounds possess activity of antagonist of gonadotropin-releasing hormone that allows their using in pharmaceutical compositions. Also, invention describes methods for synthesis of these compounds.
EFFECT: improved method of synthesis, valuable medicinal properties of compounds and pharmaceutical composition.
22 cl, 1 tbl, 32 ex

Description

Текст описания приведен в факсимильном виде.

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Claims (24)

1. Соединение общей формулы (I)1. The compound of General formula (I)
Figure 00000157
Figure 00000157
 в котором радикал R1означает атом водорода, линейный, разветвленный или циклический C1-С6алкил и может быть необязательно замещенным группами арил, гетероарил или -COOR11, где арил или гетероарил может быть замещенным, имея вплоть до трех заместителей, которые независимо выбраны из группы, включающей -NO2, -СН3, -CF3, -ОСН3, -OCF3 и атомы галогена;in which the radical R 1 means a hydrogen atom, a linear, branched or cyclic C 1 -C 6 alkyl and may be optionally substituted by aryl, heteroaryl or —COOR 11 groups, where the aryl or heteroaryl may be substituted with up to three substituents which are independently selected from the group consisting of —NO 2 , —CH 3 , —CF 3 , —OCH 3 , —OCF 3, and halogen atoms; радикал R11означает атом водорода, линейный, разветвленный или циклический C1-C12 алкил, С1-С12аралкил, арил, гетероарил или -СОСН3, и может быть необязательно замещенным одним заместителем, выбранным из группы, включающей -CONH2, -СОСН3, -СООСН3, -SO2CH3 и арил;the radical R 11 means a hydrogen atom, a linear, branched or cyclic C 1 -C 12 alkyl, C 1 -C 12 aralkyl, aryl, heteroaryl or —COCH 3 , and may be optionally substituted with one substituent selected from the group consisting of —CONH 2 , —COCH 3 , —COOCH 3 , —SO 2 CH 3 and aryl; радикалы R2, R3, R4 и R5 каждый независимо означает атом водорода, галогена, группы -СООН, -CONH2, -CF3, -OCF3, -NO2, линейный, разветвленный или циклический C1-С6алкил, C1-С6алкокси, С1-С12аралкил, арил или гетероарил;the radicals R 2 , R 3 , R 4 and R 5 each independently mean a hydrogen atom, a halogen atom, a —COOH group, —CONH 2 , —CF 3 , —OCF 3 , —NO 2 group, a linear, branched or cyclic C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 12 aralkyl, aryl or heteroaryl; радикал R6 означает группу -CONR8R9, -COOR8, -CH2NR8R9, -CH2R8, -CH2OR8;the radical R 6 means a group —CONR 8 R 9 , —COOR 8 , —CH 2 NR 8 R 9 , —CH 2 R 8 , —CH 2 OR 8 ; где радикалы R8 и R9 каждый независимо означает атом водорода, линейный, разветвленный или циклический С1-С12алкил, С1-С12аралкил, C1-С12 гетаралкил, арил, или гетероарил, каждый из которых может быть замещенным одним или более заместителями, выбранными из группы, включающей -ОН, -NH2, -CONHR10, -COOR10, -NH-C(=NH)-NH2 и галоген;where the radicals R 8 and R 9 each independently mean a hydrogen atom, a linear, branched or cyclic C 1 -C 12 alkyl, C 1 -C 12 aralkyl, C 1 -C 12 hetaralkyl, aryl, or heteroaryl, each of which may be substituted one or more substituents selected from the group consisting of —OH, —NH 2 , —CONHR 10 , —COOR 10 , —NH — C (= NH) —NH 2, and halogen; где радикал R10 означает атом водорода, линейный, разветвленный или циклический C1-C12 алкил, С1-С12аралкил, арил или гетероарил и необязательно замещен группой -CON(R11)2 илиwhere the radical R 10 means a hydrogen atom, a linear, branched or cyclic C 1 -C 12 alkyl, C 1 -C 12 aralkyl, aryl or heteroaryl and is optionally substituted with a group -CON (R 11 ) 2 or где радикалы R8 и R9 вместе с атомом азота, с которым они связаны, образуют гетероциклическую структуру;where the radicals R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclic structure; радикал R7 означает атом водорода, линейный, разветвленный или циклический С1-С12алкил, С1-С12аралкил, арил, или гетероарил, группу -NR12R13, -NHCOR14, -NHCONHR14, -NHCOOR14 или -NHSO2R14 и может быть необязательно замещенным одним или более заместителями, выбранными из группы, включающей -ОН, -NH2, -CONH2, -СООН и галоген;the radical R 7 means a hydrogen atom, linear, branched or cyclic C 1 -C 12 alkyl, C 1 -C 12 aralkyl, aryl, or heteroaryl, the group —NR 12 R 13 , —NHCOR 14 , —NHCONHR 14 , —NHCOOR 14 or —NHSO 2 R 14 and may optionally be substituted with one or more substituents selected from the group consisting of —OH, —NH 2 , —CONH 2 , —COOH, and halogen; каждый из радикалов R12 и R13 независимо означает атом водорода, линейный, разветвленный или циклический С1-С12алкил и может быть необязательно замещен одним или более из следующих заместителей: арил или гетероарил, которые, в свою очередь, могут содержать вплоть до трех заместителей, независимо выбранных из группы, включающей -NO2, -СН3, -CF3, -ОСН3, -OCF3 и галоген, иeach of the radicals R 12 and R 13 independently means a hydrogen atom, a linear, branched or cyclic C 1 -C 12 alkyl and may optionally be substituted by one or more of the following substituents: aryl or heteroaryl, which, in turn, may contain up to three substituents independently selected from the group consisting of —NO 2 , —CH 3 , —CF 3 , —OCH 3 , —OCF 3 and halogen, and радикал R14 означает атом водорода, линейный, разветвленный или циклический С1-С12алкил, С1-С12аралкил, арил или гетероарил, который может быть необязательно замещен одним или более заместителями, выбранными из группы, включающей -NO2, -СН3, -OR11, -CF3, -OCF3, -ОН, -N(R11)2, -OCOR11, -СООН, -CONH2, -NHCONHR11, -NHCOOR11 и галоген;the radical R 14 means a hydrogen atom, linear, branched or cyclic C 1 -C 12 alkyl, C 1 -C 12 aralkyl, aryl or heteroaryl, which may be optionally substituted with one or more substituents selected from the group consisting of —NO 2 , - CH 3 , —OR 11 , —CF 3 , —OCF 3 , —OH, —N (R 11 ) 2 , —OCOR 11 , —COOH, —CONH 2 , —NHCONHR 11 , —NHCOOR 11, and halogen; каждый из радикалов Ra, Rb, Rc, Rd, Re и Rf независимо означает атом водорода, атом галогена, группу СООН, -CONH2, -CF3, -OCF3, -NO2, линейный, разветвленный или циклический -C1-С6алкил, -C1-С6алкокси, арил или гетероарил; причем гетероарил и гетероциклическая группа там, где она присутствует, означает пиридинил, пирролидинил, индолил;each of the radicals R a , R b , R c , R d , R e and R f independently means a hydrogen atom, a halogen atom, a COOH group, —CONH 2 , —CF 3 , —OCF 3 , —NO 2 , linear, branched or cyclic -C 1 -C 6 alkyl, -C 1 -C 6 alkoxy, aryl or heteroaryl; wherein the heteroaryl and heterocyclic group, where present, are pyridinyl, pyrrolidinyl, indolyl; при условии, что соединение общей формулы I выбрано не из группы, включающей 3-амино-1,2,3,4-тетрагидрокарбазол-3-карбоновую кислоту, 3-амино-6-метокси-1,2,3,4-тетрагидрокарбазол-3-карбоновую кислоту, 3-амино-6-бензилокси-1,2,3,4-тетрагидрокарбазол-3-карбоновую кислоту, 3-ацетамидо-1,2,3,4-тетрагидрокарбазол-3-карбоновую кислоту, метиловый эфир 3-ацетамидо-1,2,3,4-тетрагидрокарбазол-3-карбоновой кислоты, (-)-метиловый эфир 3-ацетамидо-1,2,3,4-тетрагидрокарбазол-3-карбоновой кислоты, 3-трет-бутоксикарбониламино-1,2,3,4-тетрагидрокарбазол-3-карбоновую кислоту, 9-метил-1,2,3,4-тетрагидрокарбазол-4-карбоновой кислоты, 6-метокси-9-метил-1,2,3,4-тетрагидрокарбазол-4-карбоновой кислоты, 9-метил-1,2,3,4-тетрагидрокарбазол-4-карбоксамида, или 6-метокси-9-метил-1,2,3,4-тетрагидрокарбазол-4-карбоксамида.provided that the compound of general formula I is not selected from the group consisting 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 ester 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, (-) - 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid methyl ester, 3-tert-butoxycarbonylamino 1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, 9-methyl-1,2,3, 4-tetrahydrocarbazole-4-carboxylic acid, 6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazole-4-carboxylic acid, 9-methyl-1,2,3,4-tetrahydrocarbazole-4-carboxamide, or 6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazole-4-carboxamide. 2. Соединение по п.1, в котором радикалы Ra, Rb, Rc, Rd, Re и Rf означают атомы водорода.2. The compound according to claim 1, in which the radicals R a , R b , R c , R d , R e and R f are hydrogen atoms. 3. Соединение по п.1, в котором радикал R1означает атом водорода.3. The compound according to claim 1, in which the radical R 1 means a hydrogen atom. 4. Соединение по п.1, в котором радикалы R2, R3, R4 и/или R5 не означают атомы водорода.4. The compound according to claim 1, in which the radicals R 2 , R 3 , R 4 and / or R 5 do not mean hydrogen atoms. 5. Соединение по п.4, в котором радикалы R2, R3, R4 и R5 независимо означают -СН3, -Cl или -ОСН3.5. The compound according to claim 4, in which the radicals R 2 , R 3 , R 4 and R 5 independently mean —CH 3 , —Cl or —OCH 3 . 6. Соединение по п.5, которое выбрано из группы, включающей6. The compound according to claim 5, which is selected from the group including фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-2-метилпропил]амино]карбонил]-2,3,4,9-тетрагидро-8-метил-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenylmethyl ether [(1S, 2S) -1 - [[[((3R) -3 - [[[(1S) -1- (aminocarbonyl) -2-methylpropyl] amino] carbonyl] -2,3,4,9- tetrahydro-8-methyl-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-2-метилпропил]амино]карбонил]-6-хлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты иphenyl methyl ether [(1S, 2S) -1 - [[[[(3R) -3 - [[[(1S) -1- (aminocarbonyl) -2-methylpropyl] amino] carbonyl] -6-chloro-2,3, 4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid and фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-2-метилпропил]амино]карбонил]-2,3,4,9-тетрагидро-8-метокси-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты.phenylmethyl ether [(1S, 2S) -1 - [[[((3R) -3 - [[[(1S) -1- (aminocarbonyl) -2-methylpropyl] amino] carbonyl] -2,3,4,9- tetrahydro-8-methoxy-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid. 7. Соединение по п.1, в котором радикал R6 выбирают из группы, включающей остаток фенилаланиламида, остаток изолейциламида, остаток валил-4-аминобензамида, остаток валил-N-метиламида, радикал карбоксил, остаток карбонилвалиламида, остаток карбонилтреониламида, остаток 4-карбоксамидофенилкарбоксамида, радикал метиламинометил-2-пиридил, остатки карбонилвалинола и метилвалинола.7. The compound according to claim 1, in which the radical R 6 is selected from the group consisting of phenylalanilamide residue, isoleucamide residue, valyl-4-aminobenzamide residue, valyl-N-methylamide residue, carboxyl radical, carbonylvalamide residue, carbonyltreonylamide residue, 4- residue carboxamidophenylcarboxamide, methylaminomethyl-2-pyridyl radical, residues of carbonylvalinol and methylvalinol. 8. Соединение по п.7, которое выбрано из группы, включающей фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-2-амино-2-оксо-1-(фенилметил)этил]амино]карбонил]-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,8. The compound according to claim 7, which is selected from the group comprising phenylmethyl ether [(1S, 2S) -1 - [[[((3R) -3 - [[[(1S) -2-amino-2-oxo-1 - (phenylmethyl) ethyl] amino] carbonyl] -2,3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S,2S)-1-(аминокарбонил)-2-метилбутил]амино]карбонил]-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[[(3R) -3 - [[[(1S, 2S) -1- (aminocarbonyl) -2-methylbutyl] amino] carbonyl] -2,3,4, 9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-[[[4-(аминокарбонил)фенил]амино]карбонил]-2-метилпропил]амино]карбонил]-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[((3R) -3 - [[[(1S) -1 - [[[4- (aminocarbonyl) phenyl] amino] carbonyl] -2-methylpropyl] amino] carbonyl] -2,3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-2-метил-1-[[[(3R)-2,3,4,9-тетрагидро-3-[[[(1S)-2-метил-1-[(метиламино)карбонил]пропил]амино]карбонил]-1Н-карбазол-3-ил]амино]карбонил]бутил]карбаминовой кислоты,phenylmethyl ether [(1S, 2S) -2-methyl-1 - [[[((3R) -2,3,4,9-tetrahydro-3 - [[[(1S) -2-methyl-1 - [(methylamino ) carbonyl] propyl] amino] carbonyl] -1H-carbazol-3-yl] amino] carbonyl] butyl] carbamic acid, 2,3,4,9-тетрагидро-3-(3-фенилпропил)-O-(4-пиридинилметил)-1Н-карбазол-3-метанол,2,3,4,9-tetrahydro-3- (3-phenylpropyl) -O- (4-pyridinylmethyl) -1H-carbazole-3-methanol, 2,3,4,9-тетрагидро-3-(3-фенилпропил)-1Н-карбазол-3-карбоновую кислоту,2,3,4,9-tetrahydro-3- (3-phenylpropyl) -1H-carbazole-3-carboxylic acid, этиловыйэфир3-[2,3,4,9-тетрагидро-3-(3-фенилпропил)-1Н-карбазол-3-ил]-2-пропеновой кислоты,3- [2,3,4,9-tetrahydro-3- (3-phenylpropyl) -1H-carbazol-3-yl] -2-propenoic acid ethyl ester, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-2-метилпропил]амино]карбонил]-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenylmethyl ether [(1S, 2S) -1 - [[[((3R) -3 - [[[(1S) -1- (aminocarbonyl) -2-methylpropyl] amino] carbonyl] -2,3,4,9- tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S,2R)-1-(аминокарбонил)-2-гидроксипропил]амино]карбонил]-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[[(3R) -3 - [[[(1S, 2R) -1- (aminocarbonyl) -2-hydroxypropyl] amino] carbonyl] -2,3,4, 9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[(2S)-2-(аминокарбонил)-1-пирролидинил]карбонил]-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,[(1S, 2S) -1 - [[[[(3R) -3 - [[(2S) -2- (aminocarbonyl) -1-pyrrolidinyl] carbonyl] -2,3,4,9-tetrahydro-1H phenylmethyl] -carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[(2S)-2-(аминокарбонил)октагидро-1Н-индол-1-ил]карбонил]-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[((3R) -3 - [[(2S) -2- (aminocarbonyl) octahydro-1H-indol-1-yl] carbonyl] -2,3,4, 9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[4-(аминокарбонил)фенил]амино]карбонил]-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[(3R) -3 - [[[4- (aminocarbonyl) phenyl] amino] carbonyl] -2,3,4,9-tetrahydro-1H-carbazole-3 -yl] amino] carbonyl] -2-methylbutyl] carbamic acid, 2,3,4,9-тетрагидро-3-(3-фенилпропил)-N-(2-пиридинилметил)-1H-карбазол-3-метанамин,2,3,4,9-tetrahydro-3- (3-phenylpropyl) -N- (2-pyridinylmethyl) -1H-carbazole-3-methanamine, фенилметиловый эфир [(1S,2S)-1-[[[(3S)-3-[[[(1S)-1-(гидроксиметил)-2-метилпропил]амино]карбонил]-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[((3S) -3 - [[[(1S) -1- (hydroxymethyl) -2-methylpropyl] amino] carbonyl] -2,3,4,9- tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, 2,3,4,9-тетрагидро-N-[(1S)-1-(гидроксиметил)-2-метилпропил]-3-(3-фенилпропил)-1Н-карбазол-3-карбоксамид и2,3,4,9-tetrahydro-N - [(1S) -1- (hydroxymethyl) -2-methylpropyl] -3- (3-phenylpropyl) -1H-carbazole-3-carboxamide and (2S)-3-метил-2-[[[2,3,4,9-тетрагидро-3-(3-фенилпропил)-1Н-карбазол-3-ил]метил]амино]-1-бутанол.(2S) -3-methyl-2 - [[[2,3,4,9-tetrahydro-3- (3-phenylpropyl) -1H-carbazol-3-yl] methyl] amino] -1-butanol. 9. Соединение по любому из пп.1-5, 7, в котором радикал R7 выбран из группы, включающей радикал инданоиламино, радикал индолилацетиламино, радикал 2-нафтилацетиламино, радикал 3-пропиониламино, остаток фенилметилкарбоксамида, содержащий заместители в ароматической системе, остаток фенилгексиламина и радикал фенилпропил.9. The compound according to any one of claims 1 to 5, 7, wherein the R 7 radical is selected from the group consisting of indanoylamino radical, indolylacetylamino radical, 2-naphthylacetylamino radical, 3-propionylamino radical, phenylmethylcarboxamide residue containing substituents in the aromatic system, residue phenylhexylamine and a phenylpropyl radical. 10. Соединение по п.9, выбранное из группы, включающей10. The compound according to claim 9, selected from the group including N-[[(3R)-2,3,4,9-тетрагидро-3-[(1-оксо-2,3-дифенилпропил)амино]-1Н-карбазол-3-ил]карбонил]-L-валил-L-аспартамид,N - [[(3R) -2,3,4,9-tetrahydro-3 - [(1-oxo-2,3-diphenylpropyl) amino] -1H-carbazol-3-yl] carbonyl] -L-valyl L-aspartamide, (3R)-N-[(1S)-1-(аминокарбонил)-2-метилпропил]-3-[[(2,3-дигидро-1Н-инден-1-ил)карбонил]амино]-2,3,4,9-тетрагидро-1Н-карбазол-3-карбоксамид,(3R) -N - [(1S) -1- (aminocarbonyl) -2-methylpropyl] -3 - [[(2,3-dihydro-1H-inden-1-yl) carbonyl] amino] -2,3, 4,9-tetrahydro-1H-carbazole-3-carboxamide, (3S)-N-[(1S)-1-(аминокарбонил)-2-метилпропил]-2,3,4,9-тетрагидро-3-[(1Н-индол-3-илацетил)амино]-1Н-карбазол-3-карбоксамид,(3S) -N - [(1S) -1- (aminocarbonyl) -2-methylpropyl] -2,3,4,9-tetrahydro-3 - [(1H-indol-3-ylacetyl) amino] -1H-carbazole -3-carboxamide, (3S)-N-[(1S)-1-(аминокарбонил)-2-метилпропил]-2,3,4,9-тетрагидро-3-[(2-нафталинилацетил)амино]-1Н-карбазол-3-карбоксамид,(3S) -N - [(1S) -1- (aminocarbonyl) -2-methylpropyl] -2,3,4,9-tetrahydro-3 - [(2-naphthalenylacetyl) amino] -1H-carbazole-3-carboxamide , N-[[(3R)-2,3,4,9-тетрагидро-3-[[(2S,3S)-3-метил-1-оксо-2-[(1-оксо-3-фенилпропил)амино]пентил]амино]-1Н-карбазол-3-ил]карбонил]-L-валил-L-аспартамид,N - [[(3R) -2,3,4,9-tetrahydro-3 - [[(2S, 3S) -3-methyl-1-oxo-2 - [(1-oxo-3-phenylpropyl) amino] pentyl] amino] -1H-carbazol-3-yl] carbonyl] -L-valyl-L-aspartamide, (3R)-N-[(1S)-1-(аминокарбонил)-2-метилпропил]-2,3,4,9-тетрагидро-3-[[(4-метилфенил)ацетил]амино]-1Н-карбазол-3-карбоксамид,(3R) -N - [(1S) -1- (aminocarbonyl) -2-methylpropyl] -2,3,4,9-tetrahydro-3 - [[(4-methylphenyl) acetyl] amino] -1H-carbazole- 3-carboxamide N-[(1S)-1-(аминокарбонил)-2-метилпропил]-2,3,4,9-тетрагидро-3-[[(4-метоксифенил)ацетил]амино]-1Н-карбазол-3-карбоксамид,N - [(1S) -1- (aminocarbonyl) -2-methylpropyl] -2,3,4,9-tetrahydro-3 - [[(4-methoxyphenyl) acetyl] amino] -1H-carbazole-3-carboxamide, (3R)-N-[(1S)-1-(аминокарбонил)-2-метилпропил]-3-[[(3-бромфенил)ацетил]амино]-2,3,4,9-тетрагидро-1Н-карбазол-3-карбоксамид,(3R) -N - [(1S) -1- (aminocarbonyl) -2-methylpropyl] -3 - [[(3-bromophenyl) acetyl] amino] -2,3,4,9-tetrahydro-1H-carbazole- 3-carboxamide (3R)-N-[(1S)-1-(аминокарбонил)-2-метилпропил]-3-[[(4-фторфенил)ацетил]амино]-2,3,4,9-тетрагидро-1Н-карбазол-3-карбоксамид,(3R) -N - [(1S) -1- (aminocarbonyl) -2-methylpropyl] -3 - [[(4-fluorophenyl) acetyl] amino] -2,3,4,9-tetrahydro-1H-carbazole- 3-carboxamide (3R)-N-[(1S)-1-(аминокарбонил)-2-метилпропил]-3-[[(4-хлорфенил)ацетил]амино]-2,3,4,9-тетрагидро-1Н-карбазол-3-карбоксамид,(3R) -N - [(1S) -1- (aminocarbonyl) -2-methylpropyl] -3 - [[(4-chlorophenyl) acetyl] amino] -2,3,4,9-tetrahydro-1H-carbazole- 3-carboxamide (3R)-N-[(1S)-1-(аминокарбонил)-2-метилпропил]-2,3,4,9-тетрагидро-3-[(6-фенилгексил)амино]-1Н-карбазол-3-карбоксамид,(3R) -N - [(1S) -1- (aminocarbonyl) -2-methylpropyl] -2,3,4,9-tetrahydro-3 - [(6-phenylhexyl) amino] -1H-carbazole-3-carboxamide , 6,8-дихлор-2,3,4,9-тетрагидро-3-(3-фенилпропил)-1Н-карбазол-3-карбоновую кислоту и6,8-dichloro-2,3,4,9-tetrahydro-3- (3-phenylpropyl) -1H-carbazole-3-carboxylic acid and этиловый эфир 6,8-дихлор-2,3,4,9-тетрагидро-3-(3-фенилпропил)-1Н-карбазол-3-карбоновой кислоты.6.8-dichloro-2,3,4,9-tetrahydro-3- (3-phenylpropyl) -1H-carbazole-3-carboxylic acid ethyl ester. 11. Соединение по любому из пп.1-5, 7, или 9, в котором атом углерода, замещенный радикалами R6 и R7, при условии, что радикалы R6 и R7 объединены с образованием структурного элемента альфа-аминокарбоновой кислоты, находится в R конфигурации.11. The compound according to any one of claims 1 to 5, 7, or 9, in which the carbon atom substituted by the radicals R 6 and R 7 , provided that the radicals R 6 and R 7 are combined to form the structural element of alpha-aminocarboxylic acid, is in R configuration. 12. Соединение по п.1, которое выбрано из группы, включающей12. The compound according to claim 1, which is selected from the group including фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-2-метилпропил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[[(3R) -3 - [[[(1S) -1- (aminocarbonyl) -2-methylpropyl] amino] carbonyl] -6,8-dichloro-2, 3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(гидроксиметил)-2-метилпропил]амино]карбонил]-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenylmethyl ether [(1S, 2S) -1 - [[[[(3R) -3 - [[[(1S) -1- (hydroxymethyl) -2-methylpropyl] amino] carbonyl] -2,3,4,9- tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, (2S)-1-[[[(3R)-3-[[(4-хлорфенил)ацетил]амино]-2,3,4,9-тетрагидро-8-метокси-1H-карбазол-3-ил]карбонил]-2-пирролидинкарбоксамид и(2S) -1 - [[[(3R) -3 - [[(4-chlorophenyl) acetyl] amino] -2,3,4,9-tetrahydro-8-methoxy-1H-carbazol-3-yl] carbonyl ] -2-pyrrolidinecarboxamide and 6,8-дихлор-2,3,4,9-тетрагидро-3-(3-фенилпропил)-N-(2-пиридинилметил)-1Н-карбазол-3-метанамин.6,8-dichloro-2,3,4,9-tetrahydro-3- (3-phenylpropyl) -N- (2-pyridinylmethyl) -1H-carbazole-3-methanamine. 13. Соединение по п.1, которое выбрано из группы, включающей фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-13. The compound according to claim 1, which is selected from the group comprising phenylmethyl ether [(1S, 2S) -1 - [[[((3R) -3 - [[[(1S) -1- (aminocarbonyl) - 2-метилпропил]амино]карбонил]-6,8-дифтор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,2-methylpropyl] amino] carbonyl] -6,8-difluoro-2,3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S,2S)-1-(аминокарбонил)-2-метилбутил]амино]карбонил]-8-метокси-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[[(3R) -3 - [[[(1S, 2S) -1- (aminocarbonyl) -2-methylbutyl] amino] carbonyl] -8-methoxy-2, 3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S,2S)-1-(аминокарбонил)-2-метилбутил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[((3R) -3 - [[[(1S, 2S) -1- (aminocarbonyl) -2-methylbutyl] amino] carbonyl] -6,8-dichloro- 2,3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-3-метилбутил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[[(3R) -3 - [[[(1S) -1- (aminocarbonyl) -3-methylbutyl] amino] carbonyl] -6,8-dichloro-2, 3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-2-циклогексилэтил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[[(3R) -3 - [[[(1S) -1- (aminocarbonyl) -2-cyclohexylethyl] amino] carbonyl] -6,8-dichloro-2, 3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-2,2-диметилпропил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[((3R) -3 - [[[(1S) -1- (aminocarbonyl) -2,2-dimethylpropyl] amino] carbonyl] -6,8-dichloro- 2,3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-3-фенилпропил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил] карбаминовой кислоты,phenylmethyl ester [(1S, 2S) -1 - [[[((3R) -3 - [[[(1S) -1- (aminocarbonyl) -3-phenylpropyl] amino] carbonyl] -6,8-dichloro-2, 3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-2-метилбутил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-циклогексилметил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[[(3R) -3 - [[[(1S) -1- (aminocarbonyl) -2-methylbutyl] amino] carbonyl] -6,8-dichloro-2, 3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-cyclohexylmethyl] carbamic acid, фенилметиловый эфир [(1S,2S)-1-[[[(3R)-3-[[[(1S,2S)-1-(карбокси)-2-метилбутил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S, 2S) -1 - [[[((3R) -3 - [[[(1S, 2S) -1- (carboxy) -2-methylbutyl] amino] carbonyl] -6,8-dichloro- 2,3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2-methylbutyl] carbamic acid, фенилметиловый эфир [(1S)-1-[[[(3R)-3-[[[(1S,2S)-1-(аминокарбонил)-2-метилбутил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-2-(4-гидроксифенил)этил]карбаминовой кислоты,phenyl methyl ether [(1S) -1 - [[[(3R) -3 - [[[(1S, 2S) -1- (aminocarbonyl) -2-methylbutyl] amino] carbonyl] -6,8-dichloro-2, 3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -2- (4-hydroxyphenyl) ethyl] carbamic acid, фенилметиловый эфир [(1S)-1-[[[(3R)-3-[[[(1S,2S)-1-(аминокарбонил)-2-метилбутил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-3-(4-гидроксифенил)пропил]карбаминовой кислоты,phenyl methyl ether [(1S) -1 - [[[(3R) -3 - [[[(1S, 2S) -1- (aminocarbonyl) -2-methylbutyl] amino] carbonyl] -6,8-dichloro-2, 3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -3- (4-hydroxyphenyl) propyl] carbamic acid, фенилметиловый эфир [(1S)-1-[[[(3R)-3-[[[(1S,2S)-1-(аминокарбонил)-2-метилбутил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-3-фенилпропил]карбаминовой кислоты,phenyl methyl ether [(1S) -1 - [[[(3R) -3 - [[[(1S, 2S) -1- (aminocarbonyl) -2-methylbutyl] amino] carbonyl] -6,8-dichloro-2, 3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -3-phenylpropyl] carbamic acid, фенилметиловый эфир [(1S)-1-[[[(3R)-3-[[[(1S,2S)-1-(аминокарбонил)-2-метилбутил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-3-метилбутил]карбаминовой кислоты,phenyl methyl ether [(1S) -1 - [[[(3R) -3 - [[[(1S, 2S) -1- (aminocarbonyl) -2-methylbutyl] amino] carbonyl] -6,8-dichloro-2, 3,4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -3-methylbutyl] carbamic acid, фенилметиловый эфир [(1S)-1-[[[(3R)-3-[[[(1S)-1-(аминокарбонил)-3-метилбутил]амино]карбонил]-6,8-дихлор-2,3,4,9-тетрагидро-1Н-карбазол-3-ил]амино]карбонил]-3-метилбутил]карбаминовой кислоты.phenyl methyl ether [(1S) -1 - [[[(3R) -3 - [[[(1S) -1- (aminocarbonyl) -3-methylbutyl] amino] carbonyl] -6,8-dichloro-2,3, 4,9-tetrahydro-1H-carbazol-3-yl] amino] carbonyl] -3-methylbutyl] carbamic acid. 14. Фармацевтическая композиция, обладающая активностью антагониста гонадотропин-рилизинг-гормона, содержащая терапевтически эффективное количество по крайней мере одного соединения по любому из пп.1-13.14. A pharmaceutical composition having a gonadotropin releasing hormone antagonist activity comprising a therapeutically effective amount of at least one compound according to any one of claims 1 to 13. 15. Фармацевтическая композиция по п.14, в которой содержание соединения в стандартной дозе составляет от 1 мкг/кг до 100 мг/кг массы тела пациента.15. The pharmaceutical composition according to 14, in which the content of the compound in a standard dose is from 1 μg / kg to 100 mg / kg of body weight of the patient. 16. Способ получения соединений по п.1, в которых R7 означает водород, С1-С12алкил, С1-С12аралкил или гетероарил, отличающийся тем, что проводят конденсацию производного циклогексанона формулы II, содержащего группу G и иммобилизованного на твердой фазе SP через линкерную группу L, подходящую для образования радикала R6, значения16. The method of producing compounds according to claim 1, in which R 7 means hydrogen, C 1 -C 12 alkyl, C 1 -C 12 aralkyl or heteroaryl, characterized in that the condensation of the derivative of cyclohexanone of formula II containing group G and immobilized on the solid phase SP through a linker group L, suitable for the formation of the radical R 6 , the values которого указаны в п.1,which are indicated in paragraph 1,
Figure 00000158
Figure 00000158
 причем группа G идентична радикалу R7, а радикалы Ra-Rf имеют значения, как указано в п.1,moreover, the group G is identical to the radical R 7 , and the radicals R a -R f have the meanings as indicated in claim 1, с производным фенилгидразина формулы III, содержащим заместители R2-R5, указанные в п.1,with a phenylhydrazine derivative of formula III containing the substituents R 2 -R 5 specified in claim 1,
Figure 00000159
Figure 00000159
 в присутствии кислоты, предпочтительно уксусной кислоты, и соли металла, предпочтительно ZnCl2;in the presence of an acid, preferably acetic acid, and a metal salt, preferably ZnCl 2 ; затем осуществляют введение радикала R1 путем депротонирования полученного соединения обработкой основанием и затем контактирования с соединением R1X, где Х означает подходящую уходящую группу, предпочтительно галоген;then the radical R 1 is introduced by deprotonation of the resulting compound with a base treatment and then contacting with the compound R 1 X, where X is a suitable leaving group, preferably halogen; а на последней стадии осуществляют отщепление продукта реакции от твердой фазы SP с получением целевого продукта.and in the last step, the reaction product is cleaved from the solid phase SP to obtain the desired product. 17. Применение соединения по любому из пп.1-13 в качестве антагониста гонадотропин-рилизинг-гормона.17. The use of a compound according to any one of claims 1 to 13 as an antagonist of a gonadotropin releasing hormone. 18. Применение соединения по п.1, включая соединения, конкретно исключенные в п.1, для получения фармацевтического средства для ингибирования гонадотропин-рилизинг-гормона.18. The use of a compound according to claim 1, including compounds specifically excluded in claim 1, for the manufacture of a pharmaceutical agent for the inhibition of gonadotropin-releasing hormone. 19. Фармацевтическая композиция, обладающая активностью антагониста гонадотропин-рилизинг-гормона, содержащая терапевтически эффективное количество по крайней мере одного соединения по п.13.19. A pharmaceutical composition having a gonadotropin releasing hormone antagonist activity, comprising a therapeutically effective amount of at least one compound according to claim 13. 20. Фармацевтическая композиция по п.19, в которой содержание соединения в стандартной дозе составляет от 1 мкг до 100 мг на кг массы тела пациента.20. The pharmaceutical composition according to claim 19, in which the content of the compound in a standard dose is from 1 μg to 100 mg per kg of body weight of the patient. 21. Применение соединения по п.13 в качестве антагониста гонадотропин-рилизинг-гормона.21. The use of compounds according to item 13 as an antagonist of gonadotropin-releasing hormone. 22. Применение соединения по п.13 для получения фармацевтического средства для ингибирования гонадотропин-рилизинг-гормона.22. The use of the compound according to item 13 for the manufacture of a pharmaceutical agent for the inhibition of gonadotropin-releasing hormone. Приоритет по пунктам:Priority on points: 14.12.2001 - пп.1-12, 14-18;12/14/2001 - pp. 1-12, 14-18; 16.12.2002 - пп.13, 19-22.December 16, 2002 - pp. 13, 19-22.
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