Title of article :
Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck: Development of an expedient and divergent synthetic route and preliminary SAR
Author/Authors :
Erin F. DiMauro، نويسنده , , John Newcomb، نويسنده , , Joseph J. Nunes، نويسنده , , Jean E. Bemis، نويسنده , , Christina Boucher، نويسنده , , John L. Buchanan، نويسنده , , William H. Buckner، نويسنده , , Alan Cheng، نويسنده , , Theodore Faust، نويسنده , , Faye Hsieh، نويسنده , , Xin Huang، نويسنده , , Josie H. Lee، نويسنده , , Teresa L. Marshall، نويسنده , , Matthew W. Martin، نويسنده , , David C. McGowan، نويسنده , , Stephen Schneider، نويسنده , , Susan M. Turci، نويسنده , , Ryan D. White، نويسنده , , Xiaotian Zhu، نويسنده ,
Abstract :
4-Amino-5,6-biaryl-furo[2,3-d]pyrimidines were identified as potent non-selective inhibitors of Lck. A novel, divergent, and practical synthetic route was developed to access derivatives from bifunctional intermediates. Lead optimization was guided by X-ray crystallographic data, and preliminary SAR led to the identification of compounds with improved cellular potency and selectivity.
Keywords :
Kinase inhibitors , anti-inflammatory , Lymphocyte specific kinase (Lck) , Furopyrimidine
