Claims
- 1. Compounds of the formula ##STR16## wherein R and R.sub.9 are independently hydroxy or lower alkoxy, R.sub.1 and R.sub.2 are independently hydrogen, lower alkyl, or aryl-lower alkyl having from 7 to 12 carbon atoms,
- R.sub.3, R.sub.4, R.sub.5, R.sub.7 and R.sub.8 are hydrogen or lower alkyl,
- R.sub.6 is a heterocyclic group selected from the group consisting of pyrrolyl, pyrrolinyl, pyrrolidinyl, pyridinyl, dihydropyridinyl, piperidinyl, morpholinyl, thiomorpholinyl, imidazolyl, imidazolinyl, imidazolidinyl, furanyl, furfuryl, thienyl, benzimidazolyl, thiazolyl, thiazolinyl, thiazolidinyl, indolyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl,tetrahydroisoquinolinyl, and indolylethyl,
- and wherein
- alkyl where present can carry at least one substituent selected from the group consisting of hydroxy, lower alkoxy, thio, lower alkylmercapto, amino, lower alkylamino, di(lower alkyl) amino, halogen, and nitro;
- the heterocyclic group can carry at least one substituent selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, halogen and trifluoromethyl; and
- their pharmaceutically acceptable, nontoxic acid addition salts and where R or R.sub.9 or both are hydroxy, their pharmaceutically acceptable basic salts.
- 2. Compounds of the formula ##STR17## wherein R and R.sub.9 are independently hydroxy, lower alkoxy, lower alkenoxy, di(lower alkyl)amino-lower alkoxy, hydroxy-lower alkoxy, acylamino-lower alkoxy, acyloxy-lower alkoxy, aryloxy, aryloxy-lower alkoxy, amino, lower alkylamino, di-lower alkylamino, hydroxyamino, or aryl-lower alkylamino,
- R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.7 and R.sub.8 are independently hydrogen, alkyl having from 1 to 20 carbon atoms, alkenyl having from 2 to 20 carbon atoms, alkynyl having from 2 to 20 carbon atoms, aryl-lower alkyl having from 7 to 12 carbon atoms, or heterocyclic-lower alkyl having from 6 to 12 carbon atoms,
- R.sub.6 is a heterocyclic group,
- R.sub.2 and R.sub.3 taken together with the carbon and nitrogen to which they are respectively attached and R.sub.3 and R.sub.5 taken together with the nitrogen and carbon to which they are respectively attached may form an N-heterocycle containing from 3 to 5 carbon atoms or 2 to 4 carbon atoms and a sulfur atom, and wherein
- the alkyl, alkenyl, and alkynyl groups may carry substituents selected from the group consisting of hydroxy, lower alkoxy, thio, lower alkylmercapto, amino, lower alkylamino, di(lower alkyl)amino, halogen, and nitro;
- the heterocyclic groups are selected from the group consisting of pyrrole, pyrroline, pyrrolidine, pyridine, dihydropyridine, piperidine, morpholine, thiomorpholine, imidazole, imidazoline, imidazolidine, furan, furfuryl, thiophene, benzimidazole, thiazole, thiazoline, thiazolidine, indole, quinoline, isoquinoline, tetrahydroquinoline, tetrahydroisoquinoline, and indolylethyl,
- the heterocyclic groups may carry one or more substituents selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, hydroxy, lower alkoxy, amino, lower alkylamino, di(lower alkyl)amino, thiol, lower alkylmercapto, hydroxy-lower alkyl, amino-lower alkyl, thio-lower alkyl, nitro, halogen, sulfonamide, trifluoromethyl, methylenedioxy, ureido, and guanidino; and
- their pharmaceutically acceptable, nontoxic acid addition salts and where R or R.sub.9 or both are hydroxy, their pharmaceutically acceptable basic salts.
- 3. The compounds and salts according to claim 1 wherein R.sub.1 is lower alkyl or phenyl-lower alkyl, and R.sub.2, R.sub.3, R.sub.5, R.sub.7 and R.sub.8 are hydrogen.
- 4. The compounds and salts according to claim 3 wherein one or both of R and R.sub.9 is hydroxy.
- 5. The compounds and salts according to claim 3 wherein R is ethoxy.
- 6. The compounds and salts according to claim 5 wherein R.sub.4 is methyl.
- 7. The compounds and salts according to claim 5 wherein R.sub.1 is benzyl or phenethyl and R.sub.4 is methyl or omega-amino-n-butyl.
- 8. The compounds and salts according to claim 7 wherein R.sub.6 is indolylethyl.
- 9. The compounds and salts according to claim 7 wherein R.sub.1 is benzyl.
- 10. The compounds and salts according to claim 7 wherein R.sub.1 is phenethyl.
- 11. A method of reducing the blood pressure in hypertensive animals which comprises the administration of an antihypertensively effective amount of a compound according to claim 1.
- 12. The compound according to claim 7 which is N-(morpholin-1-yl)-[N-(N.alpha.-[(lS)-ethoxycarbonyl-3-phenylpropyl]-L-lysinyl]glycine, its lower alkyl esters, and pharmaceutically acceptable salts thereof.
- 13. The compound according to claim 7 which is N-(morpholin-1-yl)-N-[N-[(1S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]glycine, its lower alkyl esters, and pharmaceutically acceptable salts thereof.
- 14. The compound according to claim 7 which is N-(pyrrol-1-yl)-N-[N-[(1S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]glycine, its lower alkyl esters, and pharmaceutically acceptable salts thereof.
- 15. The compound according to claim 7 which is N-(thiazolidin-1-yl)-N-[N-[(1S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]glycine, its lower alkyl esters, and pharmaceutically acceptable salts thereof.
- 16. The compound according to claim 7 which is N-(piperidin-1-yl)-N-[N-[(1S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]glycine, its lower alkyl esters, and pharmaceutically acceptable salts thereof.
- 17. The compound according to claim 7 which is N-(pyrrolidin-1-yl)-N-[N-[(1S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]glycine, its lower alkyl esters, and pharmaceutically acceptable salts thereof.
- 18. The compound according to claim 7 which is N-(1,2,3,4-tetrahydroisoquinolin-2-yl)-N-[N-[(1S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]glycine, its lower alkyl esters, and pharmaceutically acceptable salts thereof.
- 19. The compound according to claim 7 which is N-(imidazol-1-yl)-N-[N-[(1S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]glycine, its lower alkyl esters, and pharmaceutically acceptable salts thereof.
- 20. The compound according to claim 7 which is N-(furfuryl)-N-[N-[(1S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]glycine, its lower alkyl esters, and pharmaceutically acceptable salts thereof.
- 21. The compound according to claim 7 which is N-(2-thienylmethylene)-N-[N-[(1S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]glycine, its lower alkyl esters, and pharmaceutically acceptable salts thereof.
- 22. The compound according to claim 7 which is N-(2-(3-indolylethyl))-N-[N-[(1S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]glycine, its lower alkyl esters, and pharmaceutically acceptable salts thereof.
- 23. A pharmaceutical preparation comprising an antihypertensive effect amount of one or more compounds or salts of claim 1 in association with a pharmaceutically acceptable carrier.
Parent Case Info
This application is a continuation-in-part of our prior copending application Ser. No. 249,053, filed Mar. 30, 1981, now abandoned.
Foreign Referenced Citations (1)
Number |
Date |
Country |
50800 |
May 1982 |
EPX |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
249053 |
Mar 1981 |
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