3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)

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• 作者：John T.-A. Hsu ; Teng-Kuang Yeh ; Shih-Chieh Yen ; Chiung-Tong Chen ; Shu-Yi Hsieh ; Tsu Hsu ; Cheng-Tai Lu ; Chun-Hwa Chen ; Ling-Hui Chou ; Ching-Hui Chiu ; Yun-I Chang ; Ya-Ju Tseng ; Kuei-Rong Yen ; Yu-Sheng Chao ; Wen-Hsing Lin ; Weir-Torn Jiaang
• 关键词：FMS-like tyrosine kinase-3 ; Inhibitor ; Acute myeloid leukemia ; Receptor tyrosine kinase ; Internal tandem duplications
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：15 July, 2012
• 年：2012
• 卷：22
• 期：14
• 页码：4654-4659
• 全文大小：963 K

文摘

A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure-activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better growth inhibition of FLT3-mutated MOLM-13 cells than FLT3 inhibitors sorafenib (2) and ABT-869 (3). In particular, compound 8d exhibited the ability to regress tumors in mouse xenograft model using MOLM-13 cells.