Claims
- 1. A method for inhibiting endothelin converting enzyme comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of the formula: ##STR8## wherein A is acetyl, pivaloyl, t-butyloxycarbonyl, benzyloxycarbonyl or phenylsulfonyl; or A is HO.sub.2 C(CH.sub.2).sub.n C(O)-- wherein n is 1 to 3; or A is R.sub.1a C(O)-- or R.sub.1a S(O).sub.2 -- wherein R.sub.1a is morpholinyl, piperazinyl or piperazinyl substituted with loweralkyl; or A is (aminoalkyl)(alkyl)aminocarbonyl, (alkylaminoalkyl)(alkyl)aminocarbonyl or (dialkylaminoalkyl)(alkyl)aminocarbonyl;
- B is --N(R.sub.4)CH(R.sub.3)C(O)-- wherein R.sub.4 is hydrogen or loweralkyl and R.sub.3 is cycloalkyl;
- C is --N(R.sub.5)CH(R.sub.6)C(O)-- wherein R.sub.5 is hydrogen or loweralkyl and R.sub.6 is loweralkyl;
- R is naphthyl or indolyl; and
- R.sub.21 is loweralkyl; or a pharmaceutically acceptable salt, ester or prodrug thereof.
- 2. The method of claim 1 wherein R.sub.6 is 2-butyl, R.sub.3 is cyclohexylmethyl and R.sub.21 is isobutyl.
- 3. A method for suppressing endothelin production comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of the formula: ##STR9## wherein A is acetyl, pivaloyl, t-butyloxycarbonyl, benzyloxycarbonyl or phenylsulfonyl; or A is HO.sub.2 C(CH.sub.2).sub.n C(O)-- wherein n is 1 to 3; or A is R.sub.1a C(O)-- or R.sub.1a S(O).sub.2 -- wherein R.sub.1a is morpholinyl, piperazinyl or piperazinyl substituted with loweralkyl; or A is (aminoalkyl)(alkyl)aminocarbonyl, (alkylaminoalkyl)(alkyl)aminocarbonyl or (dialkylaminoalkyl)(alkyl)aminocarbonyl;
- B is --N(R.sub.4)CH(R.sub.3)C(O)-- wherein R.sub.4 is hydrogen or loweralkyl and R.sub.3 is cycloalkylalkyl;
- C is --N(R.sub.5)CH(R.sub.6)C(O)-- wherein R.sub.5 is hydrogen or loweralkyl and R.sub.6 is loweralkyl;
- R is naphthyl or indolyl; and
- R.sub.21 is loweralkyl; or a pharmaceutically acceptable salt, ester or prodrug thereof.
- 4. The method of claim 3 wherein R.sub.6 is 2-butyl, R.sub.3 is cyclohexylmethyl and R.sub.21 is isobutyl.
- 5. A compound of the formula: ##STR10## wherein A is acetyl, pivaloyl, t-butyloxycarbonyl, benzyloxycarbonyl or phenylsulfonyl; or A is HO.sub.2 C(CH.sub.2).sub.n C(O)-- wherein n is 1 to 3; or A is R.sub.1a C(O)-- or R.sub.1a S(O).sub.2 -- wherein R.sub.1a is morpholinyl, piperazinyl or piperazinyl substituted with loweralkyl; or A is (aminoalkyl)(alkyl)aminocarbonyl, (alkylaminoalkyl)(alkyl)aminocarbonyl or (dialkylaminoalkyl)(alkyl)aminocarbonyl;
- B is --N(R.sub.4)CH(R.sub.3)C(O)-- wherein R.sub.4 is hydrogen or loweralkyl and R.sub.3 is cycloalkylalkyl;
- C is --N(R.sub.5)CH(R.sub.6)C(O)-- wherein R.sub.5 is hydrogen or loweralkyl and R.sub.6 is loweralkyl;
- R is naphthyl or indolyl; and
- R.sub.21 is loweralkyl; or a pharmaceutically acceptable salt, ester or prodrug thereof.
- 6. The compound of claim 5 wherein R.sub.6 is 2-butyl, R.sub.3 is cyclohexylmethyl and R.sub.21 is isobutyl.
- 7. A method for treating hypertension comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 5.
- 8. A compound selected from the group consisting of:
- (2S,3R,4S)-2-(N-Boc-Cyclohexylalanyl-Isoleucyl-Amino)-1-(2-naphthyl-3,4-dihydroxy -6-methylheptane;
- (2S,3R,4S)-2-(N-Boc-Cyclohexylalanyl-Isoleucyl-Amino)-1-(1-naphthyl-3,4-dihydroxy -6-methylheptane;
- (2S,3R,4S)-2-(N-Boc-Cyclohexylalanyl-Isoleucyl-Amino)-1-(3-indolyl-3,4-dihydroxy -6-methylheptane;
- (2S,3R,4S)-2-{(N-(4-Methylpiperazin-1-yl-carbonyl)-Cyclohexylalanyl-Isoleucyl)amino}-1-(2-naphthyl)-3,4-dihydroxy-6-methylheptane;
- (2S,3R,4S)-2-{(N-Succinyl-Cyclohexylalanyl-Isoleucyl)amino}-1-(2-naphthyl)-3,4-dihydroxy-6-methylheptane;
- (2S,3R,4S)-2-{(N-Acetyl-Cyclohexylalanyl-Isoleucyl)amino}-1-(2-naphthyl)-3,4-dihydroxy-6-methylheptane;
- (2S,3R,4S)-2-{(N-(Morpholin-1-yl-carbonyl)-Cyclohexylalanyl-Isoleucyl)amino}-1-(2-naphthyl)-3,4-dihydroxy-6-methylheptane;
- (2S,3R,4S)-2-{({N-(N,N-Dimethylaminoethyl)-N-methylamino}carbonyl-Cyclohexylalanyl-Isoleucyl)amino}-1-(2-naphthyl)-3,4-dihydroxy-6-methylheptane; and
- (2S,3R,4S)-2-{(N-(4-Methylpiperazin-1-yl-sulfonyl)-Cyclohexylalanyl-Isoleucyl)amino}-1-(2-naphthyl)-3,4-dihydroxy-6-methylheptane; or a pharmaceutically acceptable salt, ester or prodrug thereof.
Parent Case Info
This is a continuation of U.S. patent application Ser. No. 696,487, filed May 6, 1991 and now abandoned, which is a continuation-in-part of U.S. patent application Ser. No. 649,649, filed Jan. 31, 1991 and now abandoned.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4855286 |
Wagner et al. |
Aug 1989 |
|
4981950 |
Masaki et al. |
Jan 1991 |
|
Continuations (1)
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Number |
Date |
Country |
Parent |
696487 |
May 1991 |
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Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
649649 |
Jan 1991 |
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