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Synthesis and biological evaluation of substituted benzoxazoles as inhibitors of mPGES-1: use of a conformation-based hypothesis to facilitate compound design.

Abstract：

:Microsomal prostaglandin E(2) synthase-1 (mPGES-1) is a novel therapeutic target for the treatment of inflammation and pain. In the preceding letter, we detailed the discovery of clinical candidate PF-04693627, a potent mPGES-1 inhibitor possessing a novel benzoxazole structure. While PF-04693627 was undergoing further preclinical profiling, we sought to identify a back-up mPGES-1 inhibitor that differentiated itself from PF-04693627. The design, synthesis, mPGES-1 activity and in vivo PK of a novel set of substituted benzoxazoles are described herein. Also described is a conformation-based hypothesis for mPGES-1 activity based on the preferred conformation of the cyclohexane ring within this class of inhibitors.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Walker DP,Arhancet GB,Lu HF,Heasley SE,Metz S,Kablaoui NM,Franco FM,Hanau CE,Scholten JA,Springer JR,Fobian YM,Carter JS,Xing L,Yang S,Shaffer AF,Jerome GM,Baratta MT,Moore WM,Vazquez ML

doi

10.1016/j.bmcl.2012.11.107

subject

Has Abstract

pub_date

2013-02-15 00:00:00

pages

1120-6

issue

4

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(12)01559-4

journal_volume

23

pub_type

杂志文章

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