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Xiaohui Du Ronald J. Hinklin Yumei Xiong Paul Dransfield Jaehyeon Park Todd J. Kohn Vatee Pattaropong SuJen Lai Zice Fu Xianyun Jiao David Chow Lixia Jin Jasmine Davda Murielle M. Veniant Deborah A. Anderson Brian R. Baer Josef R. Bencsik Steven A. Boyd Mark Joseph Chicarelli Peter J. Mohr Bin Wang Kevin R. Condroski Walter E. DeWolf Marion Conn Thanhvien Tran Jerry Yang Thomas D. Aicher Julio C. Medina Peter Coward Jonathan B. Houze 《ACS medicinal chemistry letters》2014,5(12):1284-1289
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F Gonzalez-Lopez de Turiso Y Shin M Brown M Cardozo Y Chen D Fong X Hao X He K Henne YL Hu MG Johnson T Kohn J Lohman HJ McBride LR McGee JC Medina D Metz K Miner D Mohn V Pattaropong J Seganish JL Simard S Wannberg DA Whittington G Yu TD Cushing 《Journal of medicinal chemistry》2012,55(17):7667-7685
Structure-based rational design led to the synthesis of a novel series of potent PI3K inhibitors. The optimized pyrrolopyridine analogue 63 was a potent and selective PI3Kβ/δ dual inhibitor that displayed suitable physicochemical properties and pharmacokinetic profile for animal studies. Analogue 63 was found to be efficacious in animal models of inflammation including a keyhole limpet hemocyanin (KLH) study and a collagen-induced arthritis (CIA) disease model of rheumatoid arthritis. These studies highlight the potential therapeutic value of inhibiting both the PI3Kβ and δ isoforms in the treatment of a number of inflammatory diseases. 相似文献
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