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

  • Bioorg Med Chem Lett. 2012 Jul 15;22(14):4654-9. doi: 10.1016/j.bmcl.2012.05.116.
John T-A Hsu  1 ,  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
Affiliations
  • 1. Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Rd., Zhunan Town, Miaoli Country 350, Taiwan, ROC.
PMID: 22726931 DOI: 10.1016/j.bmcl.2012.05.116
Abstract

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.