Claims
- 1. A compound of the formula: ##STR9## wherein R.sub.1 is 4-piperazinyl, 1-methyl-4-piperazinyl, 1-methyl-1-oxo-4-piperazinyl, 2-oxo-4piperazinyl or 1-methyl-4-homopiperazinyl;
- R.sub.2 is benzyl, 2-phenylethyl, 1-naphthylmethyl or 2-naphthylmethyl;
- R.sub.3 is 4-thiazolyl, 2-amino-4-thiazolyl, 2-thiazolyl, 5-thiazolyl, 1-pyrazolyl, 3-pyrazolyl or 1-imidazolyl;
- R.sub.4 is isobutyl or cyclopropyl;
- R.sub.5 is hydrogen or loweralkyl; and
- X is CH.sub.2 ; or a pharmaceutically acceptable salt, ester or prodrug thereof.
- 2. The compound of claim 1 wherein R.sub.2 is benzyl and R.sub.3 is 4-thiazolyl, 2-amino-4-thiazolyl, 2-thiazolyl or 5-thiazolyl.
- 3. A compound of the formula: ##STR10## wherein R.sub.1 is 4-piperazinyl, 1-methyl-4-piperazinyl, 1-methyl-1-oxo-4-piperazinyl, 2-oxo-4-piperazinyl or 1-methyl-4-homopiperazinyl;
- R.sub.2 is benzyl, 2-phenylethyl, 1-naphthylmethyl or 2-naphthylmethyl;
- R.sub.3 is 4-thiazolyl or 2-amino-4-thiazolyl;
- R.sub.4 is isobutyl or cyclopropyl; and
- R.sub.5 is hydrogen or loweralkyl; or a pharmaceutically acceptable salt, ester or prodrug thereof.
- 4. The compound of claim 3 wherein R.sub.1 is 1-methyl-4-piperazinyl, R.sub.2 is benzyl and R.sub.3 is 4-thiazolyl or 2-amino-4-thiazolyl.
- 5. (2S)-2-Benzyl-3-(1-methyl-piperazin-4-ylsulfonyl)propionyl-(L)-(4-Thiazolyl)Ala Amide of (2S,3R,4S)-2-Amino-1-cyclohexyl-3,4-dihydroxy-6methylheptane; or a pharmaceutically acceptable salt, ester or prodrug thereof.
- 6. (2S)-2-Benzyl-3-(1-methyl-piperazin-4-ylsulfonyl)propionyl-(L)-(4-Thiazolyl)Ala Amide of (2S,3R,4S)-2-Amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane hydrochloride.
- 7. A compound selected from the group consisting of: 2S)-2-Benzyl-3-(1-methylpiperazin-4-ylsulfonyl)propionyl-(L)-(2-aminothiazol-4-yl)Ala Amide of (2S,3R,4S)-2-Amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane; (2S)-2-Benzyl-3-(1-methylpiperazin-4-ylsulfonyl)propionyl-(L)-(4-Thiazolyl)Ala Amide of (2S,3R,4S)-2-Amino-1-cyclohexyl-3,4-dihydroxy-4-(cyclopropyl)butane; and (2S)-2-Benzyl-3-(1-methylpiperazin-4-ylsulfonyl)propionyl-(L)-(2-aminothiazol-4-yl)Ala Amide of (2S,3R,4S)-2-Amino-1-cyclohexyl-3,4-dihydroxy-4-(cyclopropyl)butane; or a pharmaceutically acceptable salt, ester or prodrug thereof.
- 8. A method for inhibiting renin comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1.
- 9. A pharmaceutical composition for treating hypertension or congestive heart failure, comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 1.
- 10. A method for treating hypertension or congestive heart failure comprising administering to a mammal in need a therapeutically effective amount of a compound or claim 1.
- 11. A method for treating hypertension or congestive heart failure comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1 in combination with another cardiovascular agent.
- 12. A pharmaceutical composition for treating hypertension or congestive heart failure comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 1 in combination with another cardiovascular agent.
- 13. A pharmaceutical composition for treating hypertension or congestive heart failure, comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 5.
- 14. A method for treating hypertension or congestive heart failure comprising administering to a mammal in need a therapeutically effective amount of a compound of claim 5.
- 15. (2S)-2-Benzyl-3-(1-methyl-piperazin-4-ylsulfonyl)propionyl-(L)-4-Thiazolyl)Ala Amide of (2S,3R,4S)-2-Amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane methanesulfonate.
- 16. A method for inhibiting renin comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 3.
- 17. A pharmaceutical composition for treating hypertension or congestive heart failure, comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 3.
- 18. A method for treating hypertension or congestive heart failure comprising administering to a mammal in need a therapeutically effective amount of a compound of claim 3.
- 19. A method for treating hypertension or congestive heart failure comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 3 in combination with another cardiovascular agent.
- 20. A pharmaceutical composition for treating hypertension or congestive heart failure, comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 3 in combination with another cardiovascular agent.
- 21. A method for inhibiting renin comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 5.
- 22. A method for treating hypertension or congestive heart failure comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 5 in combination with another cardiovascular agent.
- 23. A pharmaceutical composition for treating hypertension or congestive heart failure, comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 5 in combination with another cardiovascular agent.
- 24. A method for inhibiting renin comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 6.
- 25. A pharmaceutical composition for treating hypertension or congestive heart failure, comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 6.
- 26. A method for treating hypertension or congestive heart failure comprising administering to a mammal in need a therapeutically effective amount of a compound of claim 6.
- 27. A method for treating hypertension or congestive heart failure comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 6 in combination with another cardiovascular agent.
- 28. A pharmaceutical composition for treating hypertension or congestive heart failure, comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 6 in combination with another cardiovascular agent.
Parent Case Info
This is a continuation of U.S. patent application Ser. No. 683,663, filed Apr. 15, 1991, which is a continuation-in-part of U.S. patent application Ser. No. 564,925, filed Aug. 9, 1990, which is a continuation-in-part of U.S. patent application Ser. No. 522,349, filed May 11, 1990 all are now abandoned.
US Referenced Citations (6)
Foreign Referenced Citations (11)
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Continuations (1)
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Number |
Date |
Country |
Parent |
683663 |
Apr 1991 |
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Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
564925 |
Aug 1990 |
|
Parent |
522349 |
May 1990 |
|