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Engler, Thomas A; Henry, James R; Malhotra, Sushant; Cunningham, Brian; Furness, Kelly; Brozinick, Joseph; Burkholder, Timothy P; Clay, Michael P; Clayton, Joshua; Diefenbacher, Clive; Hawkins, Eric; Iversen, Philip W; Li, Yihong; Lindstrom, Terry D; Marquart, Angela L; McLean, Johnathan; Mendel, David; Misener, Elizabeth; Briere, Daniel; O'Toole, John C; Porter, Warren J; Queener, Steven; Reel, Jon K; Owens, Rebecca A; Brier, Richard A; Eessalu, Thomas E; Wagner, Jill R; Campbell, Robert M; Vaughn, Renee
Journal of medicinal chemistry, 07/2004, Letnik: 47, Številka: 16Journal Article
Glycogen synthase kinase-3 (GSK3) is involved in signaling from the insulin receptor. Inhibitors of GSK3 are expected to effect lowering of plasma glucose similar to insulin, making GSK3 an attractive target for the treatment of type 2 diabetes. Herein we report the discovery of a series of potent and selective GSK3 inhibitors. Compounds 7 − 12 show oral activity in an in vivo model of type II diabetes, and 9 and 12 have desirable PK properties.
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