Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors

…, S Sun, D Knighton, C Rodgers, K Rafidi, A Zou…

Index: Liu, Kevin K.C.; Huang, Xiaojun; Bagrodia, Shubha; Chen, Jeffrey H.; Greasley, Samantha; Cheng, Hengmiao; Sun, Shaoxian; Knighton, Dan; Rodgers, Caroline; Rafidi, Kristina; Zou, Aihua; Xiao, Jiezhan; Yan, Shengyong Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 4 p. 1270 - 1274

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Citation Number: 20

Abstract

Intra-molecular hydrogen bonding was introduced to the quinazoline motif to form a pseudo ring (intra-molecular H-bond scaffold, iMHBS) to mimic our previous published core structures, pyrido [2.3-D] pyrimidin-7-one and pteridinone, as PI3K/mTOR dual inhibitors. This design results in potent PI3K/mTOR dual inhibitors and the purposed intra-molecular hydrogen bonding structure is well supported by co-crystal structure in PI3Kγ enzyme. In ...