BENZOFURAN BASED ANGIOTENSIN-II ANTAGONISTS RELATED TO GR117289 - ENHANCEMENT OF POTENCY INVITRO AND ORAL ACTIVITY

被引：21

作者：

MIDDLEMISS, D

WATSON, SP

ROSS, BC

DOWLE, MD

SCOPES, DIC

MONTANA, JG

SHAH, P

HIRST, GC

PANCHAL, TA

PATON, JMS

PASS, M

HUBBARD, T

HAMBLETT, J

CARDWELL, KS

JACK, TI

STUART, G

COOTE, S

BRADSHAW, J

DREW, GM

HILDITCH, A

CLARK, KL

ROBERTSON, MJ

BAYLISS, MK

DONNELLY, M

PALMER, E

MANCHEE, GRM

机构：

[1] Glaxo Group Research, Ware

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1993年 / 3卷 / 04期

关键词：

D O I：

10.1016/S0960-894X(01)81235-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A study of structure activity relationships based on the bromobenzofuran angiotensin II antagonist GR117289 is reported. This study led to the identification of compounds with potency in vitro enhanced by ca. 10 fold. Also reported is the enhancement of the oral activity of the acid analogue (1) conferred by formation of the double ester pro-drug (2). Prodrug (2) causes marked and long-lasting falls in blood pressure after oral administration at 0.3 mg/kg in renal artery ligated hypertensive rats.

引用

页码：589 / 594

页数：6

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