Thromboxane synthetase inhibitors and antihypertensive agents. 4. N-[(1H-imidazol-1-yl)alkyl] derivatives of quinazoline-2,4(1H,3H)-diones, quinazolin-4(3H)-ones, and 1,2,3-benzotriazin-4(3H)-ones
摘要:
The quinazolinedione, quinazolinone, and 1,2,3-benzotriazinone title compounds were prepared as analogues of N-[(1H-imidazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones which were the subject of a previous report from our laboratories. These compounds were evaluated as thromboxane (TX) synthetase inhibitors and as antihypertensive agents. While each series of compounds had activity both as TX synthetase inhibitors and as antihypertensives, the best compounds were N-[(1H-imidazol-1-yl)alkyl]quinazoline-2,4(1H,3H]-diones (V). In general these compounds were all selective enzyme inhibitors at least equipotent with the standard dazoxiben. These compounds were also very active antihypertensive agents as determined in SHR. The SAR is discussed for both types of activity. Compound 20a was further evaluated for TX formation inhibiting properties in several other platelet types both in vitro and ex vivo and is between 100 and 1000 times more potent than dazoxiben.
DOI:
10.1021/jm00395a016
作为产物:
描述:
7-(1H-imidazol-1-yl)heptanenitrile 以
甲苯 为溶剂,
以to produce 7-(1H-imidazol-1-yl)heptan-1-amine as a yellow oil (12.50 g, 95% yield)的产率得到7-imidazol-1-yl-heptylamine
Inhibiton of thromboxane synthetase with 1-substituted imidazole
申请人:Ono Pharmaceutical Co., Ltd.
公开号:US04320134A1
公开(公告)日:1982-03-16
The imidazole compounds of the general formula (I): ##STR1## wherein Y is a carboxyl group, a hydroxymethyl group, an N-di or -mono alkyl substituted or unsubstituted carbamoyl group, a cyano group, or an N-di or -mono alkyl substituted or unsubstituted aminomethyl group, and n is an integer of 3 to 20; and pharmaceutically acceptable salts thereof. These compounds have a strong inhibitory effect on thromboxane synthetase from rabbit platelet microsomes, and are useful as therapeutically active agents for inflammation, hypertension, thrombus, cerebral apoplexy and asthma.
Omega-((hetero)alkyl)benz(cd)indol-2-amines useful in inhibition of thromboxane synthetase and in treatment of hypertension in warm-blooded animals are disclosed.
Thromboxane synthetase enzyme inhibiting N-[(1H-imidazol-1-yl) and
申请人:American Cyanamid Company
公开号:US04555519A1
公开(公告)日:1985-11-26
This invention concerns novel N-[(1H-imidazol-1-yl) and (1H-1,2,4-triazol-1-yl)alkyl]pyridinecarboxamides which are useful as inhibitors of thromboxane synthetase and/or as hypotensive agents in the treatment of hypertension and myocardial ischemia.
N-[(1H-imidazol-1-yl)alkyl]-1H-indolecarboxamides useful as thromboxane
申请人:American Cyanamid Company
公开号:US04619941A1
公开(公告)日:1986-10-28
This invention discloses novel N-[(1H-imidazol-1-yl)alkyl]-1H-indolecarboxamides which are useful as inhibitors of thromboxane synthetase and/or as antihypertensive agents in the treatment of hypertension and myocardial ischemia.