Discovery of novel selective HER-2 sheddase inhibitors through optimization of P1 moiety.
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.
Li
Yun-Long
YL
Incyte Corporation, Experimental Station-E336, Route 141 and Henry Clay Road, Wilmington, DE 19880, USA. yunli@incyte.com
Shi
Eric
E
Burns
David
D
Li
Yanlong
Y
Covington
Maryanne B
MB
Pan
Maxwell
M
Scherle
Peggy
P
Friedman
Steve
S
Metcalf
Brian
B
Yao
Wenqing
W
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
D002219:Carbamates; D017364:Collagenases; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases