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ID: ALA1156748
Journal: Bioorg Med Chem Lett
Title: Incorporation of water-solubilizing groups in pyrazolopyrimidine mTOR inhibitors: discovery of highly potent and selective analogs with improved human microsomal stability.
Authors: Richard DJ, Verheijen JC, Curran K, Kaplan J, Toral-Barza L, Hollander I, Lucas J, Yu K, Zask A.
Abstract: A series of highly potent and selective pyrazolopyrimidine mTOR inhibitors which contain water-solubilizing groups attached to the 6-arylureidophenyl moiety have been prepared. Such derivatives displayed superior potency to those in which these appendages were attached to alternative sites. In comparison to unfunctionalized arylureido compounds, these analogs demonstrated enhanced cellular potency and significantly improved stability towards human microsomes, resulting in an mTOR inhibitor with impressive efficacy in a xenograft model with an intermittent dosing regimen.
CiteXplore: 19896845