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ID: ALA1145317
Journal: Bioorg Med Chem Lett
Title: Hit-to-lead optimization of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of KDR kinase inhibitors.
Authors: Dinges J, Akritopoulou-Zanze I, Arnold LD, Barlozzari T, Bousquet PF, Cunha GA, Ericsson AM, Iwasaki N, Michaelides MR, Ogawa N, Phelan KM, Rafferty P, Sowin TJ, Stewart KD, Tokuyama R, Xia Z, Zhang HQ.
Abstract: A series of 1,4-dihydroindeno[1,2-c]pyrazoles was prepared and evaluated for their enzymatic inhibition of KDR kinase. Computer modeling studies revealed the importance of attaching a basic side chain in predicting the binding mode of those compounds. Further investigation of structure-activity relationships led to 19, a lead compound with an acceptable selectivity profile, activity in whole cells, and good oral efficacy in an estradiol-induced murine uterine edema model of VEGF activity.
CiteXplore: 16750628