4-Acylamino-6-arylfuro [2, 3-d] pyrimidines: potent and selective glycogen synthase kinase-3 inhibitors

…, M Nakano, H Sato, Y Miyazaki, SL Schweiker…

Index: Maeda, Yutaka; Nakano, Masato; Sato, Hideyuki; Miyazaki, Yasushi; Schweiker, Stephanie L.; Smith, Jeffery L.; Truesdale, Anne T. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 15 p. 3907 - 3911

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Citation Number: 31

Abstract

Modeling studies of a furo [2, 3-d] pyrimidine GSK-3 hit compound 1 superimposed onto the X-ray crystal structure of a legacy pyrazolo [3, 4-c] pyridazine GSK-3 inhibitor 2 led to the identification of 4-acylamino-6-arylfuro [2, 3-d] pyrimidine template 3. Synthesis of analogues based on template 3 has resulted in a number of potent and selective GSK-3β inhibitors. The most potent and selective compound was the m-pyridyl analogue 24.