Polypeptides and derivatives thereof containing oxa- and azahomocyclostatine are useful for inhibiting the angiotensinogen-cleaving action of the enzyme renin.
含有氧杂-和氮杂-同环代茶碱的多肽及其衍生物对于抑制酶类肾素的血管紧张素原裂解作用是有用的。
Renin inhibiting polypeptides and intermediates therefor
申请人:PFIZER INC.
公开号:EP0211580A2
公开(公告)日:1987-02-25
Polypeptides and derivatives thereof containing oxa- and azahomocyclostatine are useful for inhibiting the angiotensinogen-cleaving action of the enzyme renin.
The reactions between diethyl N-(t-butoxycarbonyl)phosphoramidate 1. diisopropyl azodicarboxylate (DIAD), triphenylphosphine (TPP) and primary or secondary alcohols lead to the corresponding diethyl N-alkyl-N-(t-butoxycarbonyl)phosphoramidates 2a-o. Deprotection of crude 2 by refluxing with p-toluenesulfonic acid monohydrate in ethanol affords ammonium tosylates 3a-o in moderate to good overall yields. The N-alkylation of 1 proceeds stereoselectively with complete inversion of the configuration of the alkyl group.