Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10595087 | Bioorganic & Medicinal Chemistry Letters | 2013 | 8 Pages |
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 kinases. The most potent compound synthesized is pyrazolo[4,3-d]pyrimidine 21c. Compound 21c shows a Ki of 2 nM against mTOR inhibition, remarkable selectivity (>2900Ã) over PI3 kinases, and excellent potency in cell-based assays.
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Authors
Wendy Lee, Daniel F. Ortwine, Philippe Bergeron, Kevin Lau, Lichuan Lin, Shiva Malek, Jim Nonomiya, Zhonghua Pei, Kirk D. Robarge, Stephen Schmidt, Steve Sideris, Joseph P. Lyssikatos,