Utilization of a nitrogen–sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38α MAP kinase inhibitors

S Lin, ST Wrobleski, J Hynes, S Pitt, R Zhang…

Index: Lin, Shuqun; Wrobleski, Stephen T.; Hynes Jr., John; Pitt, Sidney; Zhang, Rosemary; Fan, Yi; Doweyko, Arthur M.; Kish, Kevin F.; Sack, John S.; Malley, Mary F.; Kiefer, Susan E.; Newitt, John A.; McKinnon, Murray; Trzaskos, James; Barrish, Joel C.; Dodd, John H.; Schieven, Gary L.; Leftheris, Katerina Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 19 p. 5864 - 5868

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Citation Number: 18

Abstract

The design, synthesis, and structure–activity relationships (SAR) of a series of 2- aminothiazol-5-yl-pyrimidines as novel p38α MAP kinase inhibitors are described. These efforts led to the identification of 41 as a potent p38α inhibitor that utilizes a unique nitrogen– sulfur intramolecular nonbonding interaction to stabilize the conformation required for binding to the p38α active site. X-ray crystallographic studies that confirm the proposed ...