title: Discovery of novel selective HER-2 sheddase inhibitors through optimization of P1 moiety.
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.
authors.affiliation: Incyte Corporation, Experimental Station-E336, Route 141 and Henry Clay Road, Wilmington, DE 19880, USA. yunli@incyte.com
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Li
authors.forename: Eric
authors.initials: E
authors.lastname: Shi
authors.forename: David
authors.initials: D
authors.lastname: Burns
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Li
authors.forename: Maryanne B
authors.initials: MB
authors.lastname: Covington
authors.forename: Maxwell
authors.initials: M
authors.lastname: Pan
authors.forename: Peggy
authors.initials: P
authors.lastname: Scherle
authors.forename: Steve
authors.initials: S
authors.lastname: Friedman
authors.forename: Brian
authors.initials: B
authors.lastname: Metcalf
authors.forename: Wenqing
authors.initials: W
authors.lastname: Yao
mesh_terms: D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017364:Collagenases / Q000378:metabolism; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002219:Carbamates; D017364:Collagenases; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases