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Inhibitors of human renin with C-termini derived from amides and esters of alpha-mercaptoalkanoic acids.

Abstract：

:New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. The corresponding sulfoxide and sulfone analogues were also investigated. Some of these derivatives, including one with a stable BocPhe replacement, were relatively potent inhibitors of human plasma renin, having IC50 values below 10 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys (Macaca mulatta) at 0.06-1 mg/kg, they reduced plasma renin activity by 87-94%. However, the accompanying drop in blood pressure was of short duration.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Ashton WT,Cantone CL,Tolman RL,Greenlee WJ,Lynch RJ,Schorn TW,Strouse JF,Siegl PK

doi

10.1021/jm00093a009

keywords:

subject

Has Abstract

pub_date

1992-07-24 00:00:00

pages

2772-81

issue

15

eissn

0022-2623

issn

1520-4804

journal_volume

35

pub_type

杂志文章

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