Claims
- 1. A compound having the structural formula ##STR30## wherein (A) X is
- (1) H, CH.sub.2 OH, F, Cl, Br, CN,
- (2) CO.sub.2 R.sub.1 where R.sub.1 is hydrogen, alkyl of from one to six carbon atoms, or a pharmaceutically acceptable metal or amine cation,
- (3) CONR.sub.2 R.sub.3 where R.sub.2 and R.sub.3 are independently hydrogen or alkyl of from one to six carbon atoms, or
- (4) NR.sub.4 R.sub.5 where R.sub.4 and R.sub.5 are independently hydrogen or alkyl of from one to six carbon atoms;
- (B) W and Y are independently hydrogen or alkyl of from one to six carbon atoms;
- (C) Z is any of the following groups 1 to 6 attached to the 3- or 4-position of the phenyl ring
- (1) ##STR31## wherein A is a direct bond to the phenyl ring, (CH.sub.2).sub.n or O(CH.sub.2).sub.n+1 (where n is 1 to 4), and R.sub.6 and R.sub.7 are independently hydrogen, alkyl of from one to six carbon atoms, or hydroxyalkyl of from one to six carbon atoms;
- (2) ##STR32## wherein A is as defined above; (3) ##STR33## wherein B is a direct bond to the phenyl ring or NH, and M is NH, O, or S;
- (4) ##STR34## wherein B and M are as defined above, and R.sub.13 and R.sub.14 are independently hydrogen, alkyl or from one to six carbon atoms, R.sub.15 CHOH where R.sub.15 is hydrogen or alkyl of from one to six carbon atoms;
- (5) ##STR35## wherein B and M are as defined above; (6) ##STR36## wherein B and M are as defined above, and R.sub.16 is hydrogen, hydroxy, alkyl of from one to six carbon atoms, alkoxy of from one to six carbon atoms, --SCH.sub.3, --S(O)CH.sub.3, or --S(O.sub.2)CH.sub.3 ;
- or a pharmaceutically acceptable salt thereof.
- 2. A compound in accordance with claim 1 wherein X is hydrogen, hydroxymethyl, fluorine, bromine, or cyano, or a pharmaceutically acceptable salt thereof.
- 3. A compound in accordance with claim 1 wherein X is --CO.sub.2 R.sub.1 wherein R.sub.1 is hydrogen, alkyl of from one to six one to six carbon atoms, or a pharmaceutically acceptable metal or amine cation.
- 4. A compound in accordance with claim 1 wherein X is --CONR.sub.2 R.sub.3 where R.sub.2 and R.sub.3 are independently hydrogen or alkyl of from one to six carbon atoms, or a pharmaceutically acceptable salt thereof.
- 5. A compound in accordance with claim 1 wherein X is --NR.sub.4 R.sub.5 wherein R.sub.4 and R.sub.5 are independently hydrogen or alkyl of from one to six carbon atoms, or a pharmaceutically acceptable salt thereof.
- 6. A compound in accordance with claim 1 wherein Z is ##STR37## A is a direct bond to the phenyl ring of compound I, (CH.sub.2).sub.n or O(CH.sub.2).sub.n+1 (where n is one to four) and R.sub.6 and R.sub.7 are independently hydrogen, alkyl of from one to six carbon atoms, or a pharmaceutically acceptable salt thereof.
- 7. A compound in accordance with claim 1 wherein Z is ##STR38## or wherein A is a direct bond to the phenyl ring of compound I, (CH.sub.2).sub.n), or O(CH.sub.2).sub.n+1 (where n is one to four).
- 8. A compound in accordance with claim 1 wherein Z is ##STR39## and wherein B is a direct bond to the phenyl ring or NH, and M is NH, O, or S, or a pharmaceutically acceptable salt thereof.
- 9. A compound in accordance with claim 1 wherein Z is ##STR40## and wherein B is a direct bond to the phenyl ring or NH, and M is NH, O, or S, and R.sub.13 and R.sub.14 are independently hydrogen, alkyl of from one to six carbon atoms, R.sub.15 CHOH where R.sub.15 is hydrogen or alkyl of from one to six carbon atoms, or a pharmaceutically acceptable salt thereof.
- 10. A compound in accordance with claim 1 wherein Z is ##STR41## and wherein B is a direct bond to the phenyl ring or NH, and M is NH, O, or S, or a pharmaceutically acceptable salt thereof.
- 11. A compound in accordance with claim 1 wherein Z is ##STR42## and wherein B is a direct bond to the phenyl ring or NH, and M is NH, O, or S, and R.sub.16 is hydrogen, hydroxy, alkyl of from one to six carbon atoms, alkoxy of from one to six carbon atoms, --SCH.sub.3, --S(O)CH.sub.3, or --S(O.sub.2)CH.sub.3, or a pharmaceutically acceptable salt thereof.
- 12. A compound in accordance with claim 1 having the name 1,2-dihydro-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2-oxo-3-pyridinecarbonitrile.
- 13. A compound in accordance with claim 1 having the name 1,2-dihydro-6-methyl-2-oxo-5-[4-(4,5,6,7-tetrahydro-1H-benzimidazol-1-yl)phenyl]-3-pyridinecarbonitrile.
- 14. A compound in accordance with claim 1 having the name 1,2-dihydro-6-methyl-2-oxo-5-[4-1H-benzimidazol-1-yl)phenyl]-3-pyridinecarbonitrile.
- 15. A compound in accordance with claim 1 having the name 5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2(1H)-pyridinone.
- 16. A compound in accordance with claim 1 having the name 3-bromo-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2(1H)-pyridinone.
- 17. A compound in accordance with claim 1 having the name 3-amino-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2(1H)-pyridinone.
- 18. A pharmaceutical composition comprising a compound defined in claim 1 or a pharmaceutically acceptable salt thereof in an amount effective for treating heart failure, in combination with a pharmaceutically acceptable carrier.
- 19. A method for treating heart failure by increasing myocardial contractility in a mammal in need of such treatment comprising administering an effective amount of a pharmaceutical composition in accordance with claim 18.
- 20. A compound in accordance with claim 1 having the name 1,2-dihydro-5-[4-(1H-imidazol-1-yl]phenyl]-6-methyl-2-oxo-3-pyridinecarbonitrile monohydrochloride.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of application Ser. No. 410,803 filed Aug. 23, 1982 now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4313951 |
Lesher et al. |
Feb 1982 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
50-95264 |
Jul 1975 |
JPX |
2070606 |
Sep 1981 |
GBX |