Claims
- 1. A compound of the formula ##STR33## wherein represents a double or single bond between two carbon atoms; Q is oxygen or sulfur; R.sub.2 is hydrogen or lower alkyl; R.sub.3 is hydrogen, lower alkyl, or when represents a single bond, R.sub.3 is di-lower alkyl; R.sub.4 is hydrogen, lower alkyl or when represents a double bond, R.sub.4 is hydrogen, lower alkyl amino, cyano, CONR.sub.a R.sub.b, hydroxy, CH.sub.2 OH or ##STR34## where R.sub.a and R.sub.b are independently H or lower alkyl, R.sub.c is lower alkyl or phenyl, and n is zero to two; or R.sub.3 and R.sub.4 taken together form a ring containing one to four carbon atoms; Y is H, halogen, lower alkyl, lower alkoxy, or a group such as ##STR35## where R.sub.d and R.sub.e are independently H, lower alkyl, (CH.sub.2).sub.n R.sub.f where R.sub.f is a benzene ring optionally substituted by halogen, hydroxy, lower alkyl, lower alkoxy, and CF.sub.3, and n is zero to three, and A is any of the groups from a-e, and is attached to the 3- or 4-position of the phenyl ring:
- a. ##STR36## wherein R.sub.1, R', and R are independently hydrogen or lower alkyl, CH.sub.2 OH, SCH.sub.3, SOCH.sub.3, SO.sub.2 CH.sub.3, hydroxyalkyl, halogen, (CH.sub.2).sub.k NR", R"', wherein k is zero to two and R.sub.2 and R.sub.3 are independently hydrogen or lower alkyl, wherein lower alkyl contains one to six carbon atoms; X is a bond, or O(CH.sub.2).sub.n wherein n is two to five; with the proviso that when (i) X is a bond and is attached to the 4-position of the phenyl ring and (ii) Y is H, the groups R.sub.1, R', and R cannot be H or lower alkyl;
- b. ##STR37## where (i) W=L=Z=CH
- (ii) W=Z=N and L=CH or
- (iii) L=Z=N and W=CH
- and X is a bond, (CH.sub.2).sub.n or O(CH.sub.2).sub.n+1 wherein n is one to four;
- c. ##STR38## wherein n is one to three; or ##STR39## wherein R.sub.8 and R.sub.9 is ethylenedioxy and the pharmaceutically acceptable acid addition salts thereof; X is the same as defined in 1b, or
- d. ##STR40## wherein represents a double or single bond between two carbon atoms; R.sub.11 is hydrogen or lower alkyl; M is NH, O, or S, and X is a direct bond or ##STR41## where X, M, and R.sub.11 are the same as defined above, and the pharmaceutically acceptable acid addition salts thereof.
- 2. A compound according to claim 1 having the structure: ##STR42## where A, R.sub.2, and R.sub.3 are the same as defined in claim 1(a-d).
- 3. A compound according to claim 1 having the structure: ##STR43## wherein R.sub.1, R', X, R.sub.2, and R.sub.3 are as defined in claim 1a, and pharmaceutically acceptable acid addition salts thereof.
- 4. A compound according to claim 1 having the structure: ##STR44## wherein R.sub.1, R', R, R.sub.2, and R.sub.3 are as defined in claim 1a, and the pharmaceutically acceptable acid addition salts thereof.
- 5. A compound according to claim 1 having the structure: ##STR45## wherein W, L, Z, R.sub.2, and R.sub.3 are as defined in claim 1b, and the pharmaceutically acceptable acid addition salts thereof.
- 6. A compound according to claim 1 having the structure: ##STR46## wherein R.sub.1, R, R', R.sub.2, and R.sub.3 are as defined in claim 1a, and the pharmaceutically acceptable acid addition salts thereof.
- 7. A compound according to claim 2 having the structure: ##STR47## wherein R.sub.1, R', R, R.sub.2, and R.sub.3 are as defined in claim 2, and the pharmaceutically acceptable acid addition salts thereof.
- 8. A compound according to claim 2 having the structure: ##STR48## wherein W, L, Z, R.sub.2, and R.sub.3 are as defined in claim 2, and the pharmaceutically acceptable acid addition salts thereof.
- 9. A compound according to claim 2 having the structure: ##STR49## wherein R.sub.1, R, R', R.sub.2, and R.sub.3 are as defined in claim 2, and the pharmaceutically acceptable acid addition salts thereof.
- 10. A compound according to claim 1 having the structure: ##STR50## wherein R.sub.4 and A are as defined in claim 1a and b, and the pharmaceutically acceptable acid addition salts thereof.
- 11. A compound according to claim 10 wherein A is imidazole or imidazole substituted by lower alkyl, S-lower alkyl or CH.sub.2 OH, tetrahydrobenzimidazole, benzimidazole, or 1,2,4-triazole, and the pharmaceutically acceptable acid addition salts.
- 12. A compound according to claim 1, wherein R.sub.3 and R.sub.4 are as defined in claim 1 and A is as defined in claim 1c.
- 13. A compound according to claim 12 having the structure: ##STR51## wherein R.sub.3 is hydrogen or lower alkyl and the pharmaceutically acceptable acid addition salts thereof.
- 14. A compound according to claim 4, which is 4,5-dihydro-6-[3-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 15. A compound according to claim 5 which is 4,5-dihydro-6-[4-(1H-1,2,4-triazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 16. A compound which is 4,5-dihydro-6-[4-(1H-benzimidazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 17. A compound according to claim 6, which is 4,5-dihydro-6-[4-(4-hydroxymethyl-1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 18. A compound according to claim 6, which is 4,5-dihydro-6-[4-(2-methylthio-1H-imidazol-1-yl)-phenyl]-3(2H)-pyridazinone.
- 19. A compound according to claim 6, which is 4,5-dihydro-6-[4-(2-methylsulfinyl-1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 20. A compound according to claim 6, which is 4,5-dihydro-6-[4-(2-methylsulfonyl-1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 21. A compound according to claim 7, which is 6-[3-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 22. A compound according to claim 8, which is 6-[4-(1H-1,2,4-triazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 23. A compound according to claim 9, which is 6-[4-(4-hydroxymethyl-1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 24. A compound according to claim 9, which is 6-[4-(2-methylthio-1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 25. A compound according to claim 9, which is 6-[4-(2-methylsulfinyl-1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 26. A compound according to claim 9, which is 6-[4-(2-methylsulfonyl-1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 27. A compound which is 6-[4-(1H-benzimidazol-1-yl)phenyl]-3(2H)-pyridazinone.
- 28. A compound according to claim 9, which is 6-[4-[(4,5-dihydro-2-thiazolyl)amino]phenyl]-4,5-dihydro-3(2H)-pyridazinone.
- 29. A compound according to claim 10, which is 4-amino-6-[4-(1H)-imidazol-1-yl)-phenyl]-3(2H)-pyridazinone.
- 30. A compound according to claim 13, which is 4,5-dihydro-6-[4-[1,4-dioxa-8-azaspiro[4,5]dec-8-yl]phenyl]-3(2H)-pyridazinone.
- 31. A compound according to claim 13, which is 4,5-dihydro-6-[4-[1,4-dioxa-8-azaspiro[4,5]dec-8-yl]phenyl]-5-methyl-3(2H)-pyridazinone.
- 32. A compound according to claim 10, which is 2,3-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3-oxo-4-pyridazine carbonitrile.
- 33. A pharmaceutical composition for increasing cardiac contractility comprising an effective amount of a compound as claimed in claim 1 with a pharmaceutically acceptable carrier.
- 34. The method for increasing cardiac contractility in a patient requiring such treatment comprising administering orally or parenterally to such patients an effective amount of a compound of the Formula I ##STR52## wherein represents a double or single bond between two carbon atoms; R.sub.2 is hydrogen or lower alkyl; R.sub.3 is hydrogen, lower alkyl, or when represents a single bond, R.sub.3 is di-lower alkyl; Q is oxygen or sulfur, R.sub.4 is hydrogen, lower alkyl or when represents a double bond, R.sub.4 is hydrogen, lower alkyl, amino, cyano, CONR.sub.a R.sub.b, ##STR53## where R.sub.a and R.sub.b are independently H or lower alkyl, R.sub.c is lower alkyl or phenyl, and n is zero to two; or R.sub.3 and R.sub.4 taken together form a ring containing one to four carbon atoms; Y is H, halogen, lower alkyl, lower alkoxy, or a group such as ##STR54## where R.sub.d and R.sub.e are independently H, lower alkyl, (CH.sub.2).sub.n R.sub.f where R.sub.f is a benzene ring optionally substituted by halogen, hydroxy, lower alkyl, lower alkoxy, and CF.sub.3 and n is zero to three, and A is any of the groups from a-e, and is attached to the 3- or 4-position of the phenyl ring:
- a. ##STR55## wherein R.sub.1, R', and R are independently hydrogen or lower alkyl, CH.sub.2 OH, SCH.sub.3, SOCH.sub.3, SO.sub.2 CH.sub.3, hydroxyalkyl, halogen, (CH.sub.2).sub.k NR", R"', wherein k is zero to two and R.sub.2 and R.sub.3 are independently hydrogen or lower alkyl, wherein lower alkyl contains one to six carbon atoms; or, when attached to the 4- and 5-positions of the imidazole ring, may be taken together to form a (i) 5-, 6-, or 7-membered ring which may also contain a nitrogen atom, (ii) benzene ring which is optionally substituted by halogen, hydroxy, lower alkyl, and lower alkyloxy, and (iii) pyridine ring; X is a bond, (CH.sub.2).sub.n or O(CH.sub.2).sub.n+1 wherein n is one to four; with the proviso that when (i) X is a bond and is attached to the 4-position of the phenyl ring and (ii) Y is H, the groups R.sub.1, R', and R cannot be H or lower alkyl;
- b. ##STR56## wherein (i) W=L=X=CH
- (ii) W=Z=N and L=CH or
- (iii) L=Z=N and W=CH
- and X is the same as defined in 1a.
- c. ##STR57## wherein n is one to three; or ##STR58## wherein R.sub.8 is hydrogen and R.sub.8 and R.sub.9 are independently lower alkyl, phenyl, hydroxy, lower alkoxy, NHR.sub.17 where R.sub.17 is hydrogen, lower alkyl or lower alkanoyl, CO.sub.2 R.sub.18 where R.sub.18 is hydrogen or lower alkyl OCOB R.sub.10 where R.sub.10 is alkyl phenyl, or pyridyl and B is a direct bond or NH; or taken together are carbonyl or ethylenedioxy and the pharmaceutically acceptable acid addition salts thereof; X is the same as defined in 1a;
- d. ##STR59## wherein represents a double or single bond between two carbon atoms; R.sub.11 is hydrogen or lower alkyl; M is NH, O, or S, and X is either a direct bond or NH; or ##STR60## where X, M, and R.sub.11 are the same as defined above, and the pharmaceutically acceptable acid addition salts thereof.
CROSS-REFERENCE TO RELATED APPLICATIONS
This is a continuation-in-part application of copending U.S. patent application Ser. No. 407,973, filed Aug. 13, 1982, which is a continuation-in-part of copending U.S. patent application Ser. No. 402,488 filed July 27, 1982, which is a continuation-in-part application of U.S. patent application Ser. No. 302,181, filed Sept. 17, 1981, now U.S. Pat. No. 4,353,905.
US Referenced Citations (7)
Foreign Referenced Citations (2)
Number |
Date |
Country |
0059688 |
Feb 1982 |
EPX |
2157453 |
Nov 1971 |
DEX |
Continuation in Parts (3)
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Number |
Date |
Country |
Parent |
407973 |
Aug 1982 |
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Parent |
402488 |
Jul 1982 |
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Parent |
302181 |
Sep 1981 |
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