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

  • Bioorg Med Chem Lett. 2007 Apr 15;17(8):2305-9. doi: 10.1016/j.bmcl.2007.01.057.
Erin F DiMauro  1 ,  John Newcomb ,  Joseph J Nunes ,  Jean E Bemis ,  Christina Boucher ,  John L Buchanan ,  William H Buckner ,  Alan Cheng ,  Theodore Faust ,  Faye Hsieh ,  Xin Huang ,  Josie H Lee ,  Teresa L Marshall ,  Matthew W Martin ,  David C McGowan ,  Stephen Schneider ,  Susan M Turci ,  Ryan D White ,  Xiaotian Zhu
Affiliations
  • 1. Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA. [email protected]
PMID: 17280833 DOI: 10.1016/j.bmcl.2007.01.057
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.