Synthesis and antihypertensive activity of pyrimidin-4 (3H)-one derivatives as losartan analogue for new angiotensin II receptor type 1 (AT 1) antagonists

TW Kim, BW Yoo, JK Lee, JH Kim, KT Lee…

Index: Kim, Tae Woo; Yoo, Byoung Wook; Lee, Joon Kwang; Kim, Ji Han; Lee, Kyung-Tae; Chi, Yong Ha; Lee, Jae Yeol Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 4 p. 1649 - 1654

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Citation Number: 20

Abstract

The discovery, in vitro and in vivo studies of the highly potent AT1 antagonist 12a (BR-A- 657, Fimasartan) antagonists are presented. A series of pyrimidin-4 (3H)-one derivatives as losartan analogue were synthesized and evaluated for a novel class of AT1 receptor antagonists. Among them, 12a containing thioamido moiety displayed both high in vitro functional antagonism and binding affinity [IC50= 0.42 and 0.13 nM, respectively] and ...