1, 4-Dihydroindeno [1, 2-c] pyrazoles with acetylenic side chains as novel and potent multitargeted receptor tyrosine kinase inhibitors with low affinity for the hERG ion …

…, KL Ashworth, I Akritopoulou-Zanze…

Index: Dinges, Juergen; Albert, Daniel H.; Arnold, Lee D.; Ashworth, Kimba L.; Akritopoulou-Zanze, Irini; Bousquet, Peter F.; Bouska, Jennifer J.; Cunha, George A.; Davidsen, Steven K.; Diaz, Gilbert J.; Djuric, Stevan W.; Gasiecki, Alan F.; Gintant, Gary A.; Gracias, Vijaya J.; Harris, Christopher M.; Houseman, Kathryn A.; Hutchins, Charles W.; Johnson, Eric F.; Li, Hu; Marcotte, Patrick A.; Martin, Ruth L.; Michaelides, Michael R.; Nyein, Michelle; Sowin, Thomas J.; Su, Zhi; Tapang, Paul H.; Xia, Zhiren; Zhang, Henry Q. Journal of Medicinal Chemistry, 2007 , vol. 50, # 9 p. 2011 - 2029

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Citation Number: 36

Abstract

The synthesis of a novel series of 1, 4-dihydroindeno [1, 2-c] pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50= 3 mg/kg) superior to Sutent (ED50= 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth ...