A hit to lead discovery of novel N-methylated imidazolo-, pyrrolo-, and pyrazolo-pyrimidines as potent and selective mTOR inhibitors

…, P Bergeron, K Lau, L Lin, S Malek, J Nonomiya…

Index: Lee, Wendy; Ortwine, Daniel F.; Bergeron, Philippe; Lau, Kevin; Lin, Lichuan; Malek, Shiva; Nonomiya, Jim; Pei, Zhonghua; Robarge, Kirk D.; Schmidt, Stephen; Sideris, Steve; Lyssikatos, Joseph P. Bioorganic and Medicinal Chemistry Letters, 2013 , vol. 23, # 18 p. 5097 - 5104

Full Text: HTML

Citation Number: 12

Abstract

Abstract A series of N-7-methyl-imidazolopyrimidine inhibitors of the mTOR kinase have been designed and prepared, based on the hypothesis that the N-7-methyl substituent on imidazolopyrimidine would impart selectivity for mTOR over the related PI3Kα and δ kinases. The corresponding N-Me substituted pyrrolo [3, 2-d] pyrimidines and pyrazolo [4, 3-d] pyrimidines also show potent mTOR inhibition with selectivity toward both PI3α and δ ...