PYRIDO[2,3-D]PYRIMIDINE ANGIOTENSIN-II ANTAGONISTS

被引：44

作者：

ELLINGBOE, JW ^{[1
]}

ANTANE, M ^{[1
]}

NGUYEN, TT ^{[1
]}

COLLINI, MD ^{[1
]}

ANTANE, S ^{[1
]}

BENDER, R ^{[1
]}

HARTUPEE, D ^{[1
]}

WHITE, V ^{[1
]}

MCCALLUM, J ^{[1
]}

PARK, CH ^{[1
]}

RUSSO, A ^{[1
]}

OSLER, MB ^{[1
]}

WOJDAN, A ^{[1
]}

DINISH, J ^{[1
]}

HO, DM ^{[1
]}

BAGLI, JF ^{[1
]}

机构：

[1] WYETH AYERST RES,DIV CARDIOVASC & METAB DISORDERS,PRINCETON,NJ 08543

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 04期

关键词：

D O I：

10.1021/jm00030a013

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of pyrido[2,3-d]pyrimidine angiotensin II (A II) antagonists was synthesized and tested for antagonism of A II. Compounds with a biphenylyltetrazole pharmacophore and small alkyl groups at the 2- and ii-positions Of the pyridopyrimidine ring were found to be the most potent in an AT(1) receptor binding assay and in blocking the A II presser response in anesthetized, ganglion-blocked A II-infused rats. 5,8-Dihydro-2,4-dimethyl-8-[(2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl)methyl] pyrido[2,3-d]pyrimidin-7(6H)-one (4a) was one of the more potent compounds in the binding assay and was the most efficacious compound in the A II-infused rat model. Further study of 4a;in Goldblatt (2K-1C) rats showed the compound to have oral bioavailability and to be an efficacious and potent compound in a high renin form of hypertension.

引用

页码：542 / 550

页数：9

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