Identification of potent 5-pyrimidinyl-2-aminothiazole CDK4, 6 inhibitors with significant selectivity over CDK1, 2, 5, 7, and 9

T Shimamura, J Shibata, H Kurihara, T Mita…

Index: Shimamura, Tadashi; Shibata, Jun; Kurihara, Hideki; Mita, Takashi; Otsuki, Sachie; Sagara, Takeshi; Hirai, Hiroshi; Iwasawa, Yoshikazu Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 14 p. 3751 - 3754

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Citation Number: 30

Abstract

5-Pyrimidinyl-2-aminothiazole 1 was identified as an inhibitor of cyclin-dependent kinases (CDKs) by a screening of the Merck sample repository. The introduction of a methyl group at the C-5 or C-6 position on the pyrimidine ring, directed toward the gate keeper residue of CDK4 (Phe93), led to significant enhancement of selectivity for CDK4 over other CDKs. Compound 3 exhibited more than 300-fold selectivity for CDK4 over CDK1, 2, 5, 7, and 9. ...