NONPEPTIDE ANGIOTENSIN-II ANTAGONISTS - N-PHENYL-1H-PYRROLE DERIVATIVES ARE ANGIOTENSIN-II RECEPTOR ANTAGONISTS

被引：51

作者：

BOVY, PR ^{[1
]}

REITZ, DB ^{[1
]}

COLLINS, JT ^{[1
]}

CHAMBERLAIN, TS ^{[1
]}

OLINS, GM ^{[1
]}

CORPUS, VM ^{[1
]}

MCMAHON, EG ^{[1
]}

PALOMO, MA ^{[1
]}

KOEPKE, JP ^{[1
]}

SMITS, GJ ^{[1
]}

MCGRAW, DE ^{[1
]}

GAW, JF ^{[1
]}

机构：

[1] SEARLE & CO,CARDIOVASC DIS RES,ST LOUIS,MO 63198

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 36卷 / 01期

关键词：

D O I：

10.1021/jm00053a013

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 5-[l-[4-[(4,5-disubstituted-1H-imidazol-1-yl)methyl]-substituted]-1H-pyrrol-2-yl]-1H-tetrazoles and 5-[l-[4- [(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]-substituted] -1H-pyrrol-2-yl]-1H-tetrazoles were investigated as novel AT1-selective angiotensin II receptor antagonists. Computer-assisted modeling techniques were used to evaluate structural parameters in comparison to the related biphenyl system. New synthetic procedures have been developed to prepare the novel compounds. The best antagonists in this series had IC50 values (rat uterine membrane receptor binding) in the 10(-8) M range and corresponding pA2 in isolated organ assay (rabbit aorta rings). Structure-activity relationships indicate some similarities with the finding in the biphenyl system. Substitution on the pyrrole ring modulates activity. Compound 5 antagonized angiotensin-induced blood pressure increase when administered to conscious rat at 30 mg/kg per os.

引用

页码：101 / 110

页数：10

共 36 条

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