Identification and optimisation of novel and selective small molecular weight kinase inhibitors of mTOR

…, G Hermann, L Sebastian, M Sunose, T Presnot…

Index: Menear, Keith A.; Gomez, Sylvie; Malagu, Karine; Bailey, Christine; Blackburn, Kristel; Cockcroft, Xiao-Ling; Ewen, Sally; Fundo, Alexandra; Gall, Armelle Le; Hermann, Gesine; Sebastian, Luisa; Sunose, Mihiro; Presnot, Thomas; Torode, Eleanor; Hickson, Ian; Martin, Niall M.B.; Smith, Graeme C.M.; Pike, Kurt G. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 20 p. 5898 - 5901

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Citation Number: 55

Abstract

A pharmacophore mapping approach, derived from previous experience of PIKK family enzymes, was used to identify a hit series of selective inhibitors of the mammalian target of rapamycin (mTOR). Subsequent refinement of the SAR around this hit series based on a tri- substituted triazine scaffold has led to the discovery of potent and selective inhibitors of mTOR.