Discovery of 2-arylthieno [3, 2-d] pyrimidines containing 8-oxa-3-azabi-cyclo [3.2. 1] octane in the 4-position as potent inhibitors of mTOR with selectivity over PI3K

JC Verheijen, K Yu, L Toral-Barza, I Hollander…

Index: Verheijen, Jeroen C.; Yu, Ker; Toral-Barza, Lourdes; Hollander, Irwin; Zask, Arie Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 1 p. 375 - 379

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Citation Number: 32

Abstract

2-Aryl-4-morpholinothieno [3, 2-d] pyrimidines are known PI3K inhibitors. This class of compounds also potently inhibited the homologous enzyme mTOR. Replacement of the morpholine group in these compounds with an 8-oxa-3-azabicyclo [3.2. 1] octane group led to mTOR inhibitors with selectivity over PI3K. Optimization of the 2-aryl substituent led to the discovery of 2-(4-ureidophenyl)-thienopyrimidines as highly potent (IC50< 1nM) mTOR ...