Discovery of novel selective HER-2 sheddase inhibitors through optimization of P1 moiety

Yun-Long Li; Eric Shi; David Burns; Yanlong Li; Maryanne B Covington; Maxwell Pan; Peggy Scherle; Steve Friedman; Brian Metcalf; Wenqing Yao

doi:10.1016/j.bmcl.2009.07.052

Discovery of novel selective HER-2 sheddase inhibitors through optimization of P1 moiety

Bioorg Med Chem Lett. 2009 Sep 1;19(17):5037-42. doi: 10.1016/j.bmcl.2009.07.052. Epub 2009 Jul 25.

Authors

Yun-Long Li¹, Eric Shi, David Burns, Yanlong Li, Maryanne B Covington, Maxwell Pan, Peggy Scherle, Steve Friedman, Brian Metcalf, Wenqing Yao

Affiliation

¹ Incyte Corporation, Experimental Station-E336, Route 141 and Henry Clay Road, Wilmington, DE 19880, USA. yunli@incyte.com

PMID: 19635666
DOI: 10.1016/j.bmcl.2009.07.052

Abstract

A novel series of carbamates was discovered as potent and selective HER-2 sheddase inhibitors. Significant enhancement in potency and selectivity was achieved through attenuating the P1 moiety, which was conventionally believed to be exposed to solvent.

MeSH terms

Carbamates / chemical synthesis
Carbamates / chemistry*
Carbamates / pharmacology
Collagenases / metabolism
Humans
Microsomes, Liver / metabolism
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Receptor, ErbB-2 / antagonists & inhibitors*
Receptor, ErbB-2 / metabolism
Structure-Activity Relationship

Substances

Carbamates
Protein Kinase Inhibitors
Receptor, ErbB-2
Collagenases