| Literature DB >> 20346656 |
Timothy P Heffron1, Megan Berry, Georgette Castanedo, Christine Chang, Irina Chuckowree, Jennafer Dotson, Adrian Folkes, Janet Gunzner, John D Lesnick, Cristina Lewis, Simon Mathieu, Jim Nonomiya, Alan Olivero, Jodie Pang, David Peterson, Laurent Salphati, Deepak Sampath, Steve Sideris, Daniel P Sutherlin, Vickie Tsui, Nan Chi Wan, Shumei Wang, Susan Wong, Bing-Yan Zhu.
Abstract
Efforts to identify potent small molecule inhibitors of PI3 kinase and mTOR led to the discovery of the exceptionally potent 6-aryl morpholino thienopyrimidine 6. In an effort to reduce the melting point in analogs of 6, the thienopyrimidine was modified by the addition of a methyl group to disrupt planarity. This modification resulted in a general improvement in in vivo clearance. This discovery led to the identification of GNE-477 (8), a potent and efficacious dual PI3K/mTOR inhibitor. Copyright 2010 Elsevier Ltd. All rights reserved.Entities:
Mesh：
Substances：
Year: 2010 PMID： 20346656 DOI： 10.1016/j.bmcl.2010.03.046
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823