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Bioorg Med Chem Lett. 2009 Oct 15;19(20):5864-8. doi: 10.1016/j.bmcl.2009.08.074. Epub 2009 Aug 26.

Design and synthesis of substituted nicotinamides as inhibitors of soluble epoxide hydrolase.

Author information

1
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Rd. PO Box 368, Ridgefield, CT 06877-036, USA. steven.taylor@boehringer-ingelheim.com

Abstract

A series of potent nicotinamide inhibitors of soluble epoxides hydrolase (sEH) is disclosed. This series was designed using structure-based deconstruction and a combination of two HTS hit series, resulting in hybrid analogs that retained the optimal potency from one series, and acceptable in vitro metabolic stability from the other. Structure-guided optimization of these analogs gave rise to nanomolar inhibitors of human sEH that had acceptable plasma exposure to qualify them as probes to determine the in vivo phenotypic consequences of sEH inhibition.

PMID:
19758802
DOI:
10.1016/j.bmcl.2009.08.074
[Indexed for MEDLINE]

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