Claims for Patent: 4,470,972

Summary for Patent: 4,470,972

Title:	7-Carboxyalkylaminoacyl-1,4-dithia-7-azaspiro[4.4]-nonane-8-carboxylic acids
Abstract:	This invention relates to 7-carboxyalkyl-aminoacyl-1,4-adithia-7-azaspiro[4.4]nonane-8-carboxylic acids. The compounds of the invention are useful in the treatment of cardiovascular disorders and especially as antihypertensive agents.
Inventor(s):	Elijah H. Gold, Bernard R. Neustadt, Elizabeth M. Smith
Assignee:	Merck Sharp and Dohme LLC
Application Number:	US06/446,929
Patent Claims:	1. A compound represented by the formula ##STR6## wherein: R is a lower alkyl, benzyl, benzylthio, benzyloxy, phenylthio, or phenoxy;R1 is hydroxy or lower alkoxy; R2 is hydrogen, lower alkyl or aminoloweralkyl; and the pharmaceutically acceptable salts thereof. 2. A compound of claim 1 wherein R2 is methyl. 3. A compound of claim 2 wherein R1 is lower alkoxy. 4. A compound of claim 3 wherein R is benzyl. 5. A compound of claim 4 wherein R1 is ethoxy. 6. A compound of claim 5 which is 7-[N-(1(S)-carboethoxy-3-phenylpropyl)-(S)-alanyl]-1,4-dithia-7-azaspiro[4.4]-nonane-8(S)-carboxylic acid hydrochloride. 7. A compound of claim 2 which is 7-[N-(1(S)-carboxy-3-phenylpropyl)-(S)-alanyl]-1,4-dithia-7-azaspiro[4.4]-nonane-8(S)-carboxylic acid hydrochloride. 8. A compound of claim 2 which is 7-[N-(1(S)-carboxy-3-phenylpropyl)-(S)-alanyl]-1,4-dithia-7-azaspiro[4.4]-nonane-8(S)-carboxylic acid. 9. A compound of claim 5 which is 7-[N-(1(S)-carboethoxy-3-phenylpropyl)-(S)-alanyl]-1,4-dithia-7-azaspiro[4.4]-nonane-8(S)-carboxylic acid hemimaleate. 10. A compound of claim 1 wherein R2 is hydrogen. 11. A compound of claim 1 wherein R2 is aminobutyl. 12. A compound of claim 11 which is 7-[Nα-(1(S)-carboethoxy-3-phenylpropyl)-(S)-lysyl]-1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxylic acid dihydrochloride. 13. A compound of claim 11 which is 7-[Nα-(1(S)-carboethoxy-3-phenylpropyl)-(S)-lysyl]-1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxylic acid. 14. A compound of claim 11 which is 7-[Nα-(1(S)-carboxy-3-phenylpropyl)-(S)-lysyl]-1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxylic acid dihydrochloride. 15. A compound of claim 11 which is 7-[Nα-(1(S)-carboxy-3-phenylpropyl)-(S)-lysyl]-1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxylic acid. 16. A compound of claim 1 wherein R is benzylthio. 17. A compound of claim 1 wherein R is benzyloxy. 18. A compound of claim 1 wherein R is phenylthio. 19. A compound of claim 1 wherein R is phenyloxy. 20. A compound of claim 1 wherein R is lower alkyl. 21. A compound of claim 20 which is 7-[N-(1(S)-carboethoxypentyl)-(S)-alanyl]-1,4-dithia-7-azaspiro [4.4]-nonane-8(S)-carboxylic acid hydrochloride. 22. A compound of claim 20 which is 7-[N-(1(S)-carboethoxybutyl)-(S)-alanyl]-1,4-dithia-7-azaspiro[4.4]-nonane-8(S)-carboxylic acid hydrochloride. 23. A compound of claim 20 which is 7-[N-(1(S)-carboethoxyhexyl)-(S)-alanyl]-1,4[-dithia-7-azaspiro [4.4]-nonane-8(S)-carboxylic acid hydrochloride. 24. A compound of claim 1 wherein the pharmaceutically acceptable salts is an acid salt. 25. A compound of claim 24 wherein the acid salt is hydrochloride or hemimaleate. 26. A pharmaceutical composition comprising an antihypertensive effective amount of a compound according to claim 1 together with a pharmaceutically acceptable carrier. 27. A pharmaceutical composition comprising an antihypertensive effective amount of a compound according to claim 6 together with a pharmaceutically acceptable carrier. 28. A method of treating hypertension in mammals comprising administering to a mammal afflicted with hypertension an effective amount of a compound according to claim 1. 29. A method of treating hypertension in mammals comprising administering to a mammal afflicted with hypertension an effective amount of a compound according to claim 6.