Synthesis and biological evaluation of substituted benzoxazoles as inhibitors of mPGES-1: use of a conformation-based hypothesis to facilitate compound design.
Bioorg Med Chem Lett
; 23(4): 1120-6, 2013 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-23298810
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzoxazóis
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Oxirredutases Intramoleculares
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Inibidores Enzimáticos
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article