Structure-Based Design of Novel 2-Amino-6-phenyl-pyrimido [5′, 4′: 5, 6] pyrimido [1, 2-a] benzimidazol-5 (6 H)-ones as Potent and Orally Active Inhibitors of …

…, JJ Nunes, C Boucher, L Chai, LF Epstein…

Index: Martin, Matthew W.; Newcomb, John; Nunes, Joseph J.; Boucher, Christina; Chai, Lilly; Epstein, Linda F.; Faust, Theodore; Flores, Sylvia; Gallant, Paul; Gore, Anu; Gu, Yan; Hsieh, Faye; Huang, Xin; Kim, Joseph L.; Middleton, Scot; Morgenstern, Kurt; Oliveira-dos-Santos, Antonio; Patel, Vinod F.; Powers, David; Rose, Paul; Tudor, Yanyan; Turci, Susan M.; Welcher, Andrew A.; Zack, Debra; Zhao, Huilin; Zhu, Li; Zhu, Xiaotian; Ghiron, Chiara; Ermann, Monika; Johnston, David; Saluste, Carl-Gustaf Pierre Journal of Medicinal Chemistry, 2008 , vol. 51, # 6 p. 1637 - 1648

Full Text: HTML

Citation Number: 37

Abstract

Lck, or lymphocyte specific kinase, is a cytoplasmic tyrosine kinase of the Src family expressed in T-cells and NK cells. Genetic evidence from knockout mice and human mutations demonstrates that Lck kinase activity is critical for T-cell receptor-mediated signaling, leading to normal T-cell development and activation. A small molecule inhibitor of Lck is expected to be useful in the treatment of T-cell-mediated autoimmune and ...