Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase

…, WF Huffman, KK Koretke-Brown…

Index: Adams, Nicholas D.; Adams, Jerry L.; Burgess, Joelle L.; Chaudhari, Amita M.; Copeland, Robert A.; Donatelli, Carla A.; Drewry, David H.; Fisher, Kelly E.; Hamajima, Toshihiro; Hardwicke, Mary Ann; Huffman, William F.; Koretke-Brown, Kristin K.; Lai, Zhihong V.; McDonald, Octerloney B.; Nakamura, Hiroko; Newlander, Ken A.; Oleykowski, Catherine A.; Parrish, Cynthia A.; Patrick, Denis R.; Plant, Ramona; Sarpong, Martha A.; Sasaki, Kosuke; Schmidt, Stanley J.; Silva, Domingos J.; Sutton, David; Tang, Jun; Thompson, Christine S.; Tummino, Peter J.; Wang, Jamin C.; Xiang, Hong; Yang, Jingsong; Dhanak, Dashyant Journal of Medicinal Chemistry, 2010 , vol. 53, # 10 p. 3973 - 4001

Full Text: HTML

Citation Number: 53

Abstract

The Aurora kinases play critical roles in the regulation of mitosis and are frequently overexpressed or amplified in human tumors. Selective inhibitors may provide a new therapy for the treatment of tumors with Aurora kinase amplification. Herein we describe our lead optimization efforts within a 7-azaindole-based series culminating in the identification of GSK1070916 (17k). Key to the advancement of the series was the introduction of a 2-aryl ...