Design and synthesis of potent, isoxazole-containing renin inhibitors.

Abstract:

:The design and optimization of a novel isoxazole S(1) linker for renin inhibitor is described herein. This effort culminated in the identification of compound 18, an orally bioavailable, sub-nanomolar renin inhibitor even in the presence of human plasma. When compound 18 was found to inhibit CYP3A4 in a time dependent manner, two strategies were pursued that successfully delivered equipotent compounds with minimal TDI potential.

journal_name

Bioorg Med Chem Lett

authors

Fournier PA,Arbour M,Cauchon E,Chen A,Chefson A,Ducharme Y,Falgueyret JP,Gagné S,Grimm E,Han Y,Houle R,Lacombe P,Lévesque JF,MacDonald D,Mackay B,McKay D,Percival MD,Ramtohul Y,St-Jacques R,Toulmond S

doi

10.1016/j.bmcl.2012.03.014

subject

Has Abstract

pub_date

2012-04-15 00:00:00

pages

2670-4

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(12)00321-6

journal_volume

22

pub_type

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