New pyrazolo[1,5a]pyrimidines as orally active inhibitors of Lck

A novel series of pyrazolo[1,5a]pyrimidines was optimized to target lymphocyte-specific kinase (Lck). An efficient synthetic route was developed and SAR studies toward activity and selectivity are described, leading to Lck inhibitors with enzymatic, cellular and in vivo potency. (C) 2010 Elsevier Ltd. All rights reserved.