Author/Authors :
Yihan Wang، نويسنده , , William C. Shakespeare، نويسنده , , Wei-Sheng Huang، نويسنده , , Raji Sundaramoorthi، نويسنده , , Scott Lentini، نويسنده , , Sasmita Das، نويسنده , , Shuangying Liu، نويسنده , , Geeta Banda، نويسنده , , David Wen، نويسنده , , Xiaotian Zhu، نويسنده , , Qihong Xu، نويسنده , , Jeffrey Keats، نويسنده , , Frank Wang، نويسنده , , Scott Wardwell، نويسنده , , Yaoyu Ning، نويسنده , , Joseph T. Snodgrass، نويسنده , , Mark I. Broudy، نويسنده , , Karin Russian، نويسنده , , David Dalgarno، نويسنده , , Tim Clackson، نويسنده , , et al.، نويسنده ,
Abstract :
Novel N9-arenethenyl purines, optimized potent dual Src/Abl tyrosine kinase inhibitors, are described. The key structural feature is a trans vinyl linkage at N9 on the purine core which projects hydrophobic substituents into the selectivity pocket at the rear of the ATP site. Their synthesis was achieved through a Horner–Wadsworth–Emmons reaction of N9-phosphorylmethylpurines and substituted benzaldehydes or Heck reactions between 9-vinyl purines and aryl halides. Most compounds are potent inhibitors of both Src and Abl kinase, and several possess good oral bioavailability.
