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Discovery of a highly potent, selective, and bioavailable soluble epoxide hydrolase inhibitor with excellent ex vivo target engagement.

Authors :
Shen HC
Ding FX
Wang S
Deng Q
Zhang X
Chen Y
Zhou G
Xu S
Chen HS
Tong X
Tong V
Mitra K
Kumar S
Tsai C
Stevenson AS
Pai LY
Alonso-Galicia M
Chen X
Soisson SM
Roy S
Zhang B
Tata JR
Berger JP
Colletti SL
Source :
Journal of medicinal chemistry [J Med Chem] 2009 Aug 27; Vol. 52 (16), pp. 5009-12.
Publication Year :
2009

Abstract

4-Substituted piperidine-derived trisubstituted ureas are reported as highly potent and selective inhibitors for sEH. The SAR outlines approaches to improve activity against sEH and reduce ion channel and CYP liability. With minimal off-target activity and a good PK profile, the benchmark 2d exhibited remarkable in vitro and ex vivo target engagement. The eutomer entA-2d also elicited vasodilation effect in rat mesenteric artery.

Details

Language :
English
ISSN :
1520-4804
Volume :
52
Issue :
16
Database :
MEDLINE
Journal :
Journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
19645482
Full Text :
https://doi.org/10.1021/jm900725r