Claims
- 1. A compound of the formula: ##STR18## wherein Ring A represents a benzene ring which may be substituted by 1 to 3 substituents selected from the group consisting of an amino, mono-C.sub.1-6 alkylamino, di-C.sub.1-6 alkylamino, halogen, nitro, sulfo, cyano, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, carboxy, C.sub.1-6 alkoxy-carbonyl, formyl, acetyl, propionyl, mercapto and C.sub.1-6 alkylmercapto,
- Ring B is a benzene, cyclohexene or cyclohexane group, each of which may be substituted by 1 to 3 substituents selected from the group consisting of an amino, mono-C.sub.1-6 alkylamino, di-C.sub.1-6 alkylamino, halogen, nitro, sulfo, cyano, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, carboxy, C.sub.1-6 alkoxy-carbonyl, formyl, acetyl, propionyl, mercapto and C.sub.1-6 alkylmercapto;
- - - - represents a single bond or a double bond;
- X represents a lower alkylene, carbonyl or sulfonyl;
- Y represents a bond, oxygen, lower alkyleneoxy or a group of the formula: >N--R.sup.1 wherein R.sup.1 represents hydrogen or an alkyl group;
- R represents i) hydrogen,
- ii) (a) a C.sub.6-14 aryl group or (b) a 5- to 10-membered heteroaromatic group containing, besides carbon atoms, 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, each of which groups (a) and (b) may be substituted by 1 to 5 substituents selected from the group consisting of an amino, mono-C.sub.1-6 alkylamino, di-C.sub.1-6 alkylamino, halogen, nitro, sulfo, cyano, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, carboxy, C.sub.1-6 alkoxy-carbonyl, formyl, acetyl, propionyl, mercapto, C.sub.1-6 alkylmercapto and C.sub.6-10 aryl, or
- iii) a C.sub.1-6 alkyl group which may be substituted by 1 to 5 substituents selected from the group consisting of (a) a C.sub.6-14 aryl group and (b) a 5- to 10-membered heteroaromatic group containing, besides carbon atoms, 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur, each of which groups (a) and (b) may be substituted by 1 to 5 substituents selected from the group consisting of an amino, mono-C.sub.1-6 alkylamino, di-C.sub.1-6 alkylamino, halogen, nitro, sulfo, cyano, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, carboxy, C.sub.1-6 alkoxy-carbonyl, formyl, acetyl, propionyl, mercapto, C.sub.1-6 alkylmercapto and C.sub.6-10 aryl; and
- m and n independently represent an integer of 1 to 3, or a salt thereof.
- 2. A compound of claim 1 wherein X is a methylene, carbonyl or sulfonyl and Y is a bond, oxygen, methyleneoxy or a group of the formula: >N--R.sup.1 wherein R.sup.1 is as defined in claim 1.
- 3. A compound of claim 1 wherein X is a C.sub.1-6 alkylene, carbonyl or sulfonyl, and Y is a bond, oxygen, C.sub.1-6 alkyleneoxy or a group of the formula: >N--R.sup.1 wherein R.sup.1 is hydrogen or a C.sub.1-6 alkyl group.
- 4. A compound of claim 1 wherein Ring A is an unsubstituted benzene ring.
- 5. A compound of claim 1 wherein Ring B is an unsubstituted ring.
- 6. A compound of claim 5 wherein Ring B is a benzene ring or a cyclohexene ring.
- 7. A compound of claim 1 wherein the (a) C.sub.6-14 aryl group or (b) 5- to 10-membered heteroaromatic group containing, besides carbon atoms, 1 to 4 hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur is a phenyl group or a pyridyl group.
- 8. A compound of claim 1 wherein R is i) a phenyl or naphthyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen and C.sub.1-6 alkoxy or ii) a C.sub.1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a phenyl and pyridyl group, each of which may be substituted by 1 to 3 substituents selected from the group consisting of a halogen and C.sub.1-6 alkoxy.
- 9. A compound of claim 1 wherein X is carbonyl.
- 10. A compound of claim 1 wherein Y is oxygen or the group of the formula: >N--R.sup.1 wherein R.sup.1 is as defined in claim 1.
- 11. A compound of claim 1 wherein Y is >NH.
- 12. A compound of claim 1 wherein the group of the formula: --NH--X--Y--R is present in the 3- or 4-position of the benzene ring.
- 13. A compound of claim 1 wherein m is 1.
- 14. A compound of claim 1 wherein n is 1.
- 15. A compound of claim 1 wherein Ring A is benzene ring,
- Ring B is a benzene ring or a cyclohexene ring,
- X is a methylene, carbonyl or sulfonyl,
- Y is a bond, oxygen, methyleneoxy or a group of the formula: >N--R.sup.1, wherein
- R.sup.1 is hydrogen or a C.sub.1-6 alkyl group, and
- R is i) a phenyl or naphthyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen and C.sub.1-6 alkoxy, or
- ii) a C.sub.1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a phenyl and pyridyl group which may be substituted by 1 to 3 substituents selected from the group consisting of a halogen and C.sub.1-6 alkoxy.
- 16. A compound of claim 1 which is (3aR*,10aS*)-9-�4-(benzyloxycarbonylamino)benzyl!-4-(2H-1,3-dioxo-1,3,4,5,6,7-hexahydroisoindole-2-acetyl)-2,3,3a,4,9,10a-hexahydrobenzo�b!cyclopenta�e!�1,4!diazepin-10(1H)-one or a salt thereof.
- 17. A compound of claim 1 which is (3aR*,10aS*)-9-�4-(3-benzylureido)benzyl!-4-(phthalimidoacetyl)-2,3,3a,4,9,10a-hexahydrobenzo�b!cyclopenta�e!�1,4!diazepin-10(1H)-one or a salt thereof.
- 18. A compound of claim 1 which is (3aR*,10aS*)-9-�4-(3-benzylureido)benzyl!-4-(2H-1,3-dioxo-1,3,4,5,6,7-hexahydroisoindole-2-acetyl)-2,3,3a,4,9,10a-hexahydrobenzo�b!cyclopenta�e!�1,4!diazepin-10(1H)-one or a salt thereof.
- 19. A compound of claim 1 which is (3aR*,10aS*)-9-�4-�3-((R)-1-phenylethyl)ureido!benzyl!-4-(phthalimidoacetyl)-2,3,3a,4,9,10a-hexahydrobenzo�b!cyclopenta�e!-�1,4!diazepin-10(1H)-one or a salt thereof.
- 20. A compound of claim 1 which is (3aR*,10aS*)-9-�4-�3-(2-phenylethyl)ureido!benzyl!-4-(phthalimidoacetyl)-2,3,3a,4,9,10a-hexahydrobenzo�b!cyclopenta�e!�1,4!diazepin-10(1H)-one or a salt thereof.
- 21. A compound of claim 1 which is (3aR*,10aS*)-9-�4-�3-(4-fluorobenzyl)ureido!benzyl!-4-(phthalimidoacetyl)-2,3,3a,4,9,10a-hexahydrobenzo�b!cyclopenta�e!�1,4!diazepin-10(1H)-one or a salt thereof.
- 22. A compound of claim 1 which is (3aR*,10aS*)-9-�4-�3-(4-methoxybenzyl)ureido!benzyl!-4-(phthalimidoacetyl)-2,3,3a,4,9,10a-hexahydrobenzo�b!cyclopenta�e!�1,4!diazepin-10(1H)-one or a salt thereof.
- 23. A compound of claim 1 which is (3aR*,10aS*)-4-(phthalimidoacetyl)-9-�4-�3-(4-pyridylmethyl)ureido!-benzyl!-2,3,3a,4,9,10a-hexahydrobenzo�b!cyclopenta�e!-�1,4!diazepin-10(1H)-one or a salt thereof.
- 24. A process for producing the compound of claim 1 which comprises one of the following steps:
- i) a step of reacting a compound of the formula: ##STR19## wherein X' represents carbonyl or sulfonyl and the other symbols are as defined in claim 1 or a salt thereof with a compound of the formula: ##STR20## wherein Hal represents halogen and the other symbols are as defined in claim 1 or a salt thereof,
- ii) a step of reacting a compound of the formula: ##STR21## wherein each symbol is as defined above or a salt thereof with a compound of the formula: ##STR22## wherein M represents a metal and the other symbols are as defined above or a salt thereof,
- iii) a step of reacting a compound of the formula: ##STR23## wherein each symbol is as defined above or a salt thereof with a compound of the formula: ##STR24## wherein each symbol is as defined above or a salt thereof, iv) a step of reacting a compound of the formula: ##STR25## wherein each symbol is as defined above or a salt thereof with a compound of the formula: ##STR26## wherein each symbol is as defined above or a salt thereof in the presence of a reducing agent,
- v) a step of reacting a compound of the formula: ##STR27## wherein each symbol is as defined above or a salt thereof with a compound of the formula:
- RNCO (XVII)
- wherein R is as defined above or a salt thereof, and
- vi) a step of reacting a compound of the formula: ##STR28## wherein each symbol is as defined above or a salt thereof with a compound of the formula: ##STR29## wherein each symbol is as defined above or a salt thereof.
- 25. A pharmaceutical composition which comprises a compound of claim 1 with a pharmaceutically acceptable carrier.
- 26. Method for antagonizing gonadotropin releasing hormone receptor in mammals which comprises administrating to a subject in need a therapeutically effective amount of a compound of claim 1.
- 27. Method of claim 26 which is for sex hormone dependent diseases.
- 28. Method of claim 27 which is for treating tumors.
- 29. Method of claim 26 which is for controlling fertility.
- 30. Method of claim 26 which is for controlling menstrual cycle.
Priority Claims (1)
Number |
Date |
Country |
Kind |
7-135376 |
Jun 1995 |
JPX |
|
Parent Case Info
This application is a national stage application under 35 U.S.C. .sctn. 371 of Pct application No. JP96/01463.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/JP96/01463 |
5/30/1996 |
|
|
6/25/1996 |
6/25/1996 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO96/38438 |
12/5/1996 |
|
|
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4678784 |
Ho |
Jul 1987 |
|
Foreign Referenced Citations (3)
Number |
Date |
Country |
54-135788 |
Oct 1979 |
JPX |
17075 |
Aug 1994 |
WOX |
29900 |
Nov 1995 |
WOX |