3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3).
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.
Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Rd., Zhunan Town, Miaoli Country 350, Taiwan, ROC.
John T-A
JT
Hsu
Teng-Kuang
TK
Yeh
Shih-Chieh
SC
Yen
Chiung-Tong
CT
Chen
Shu-Yi
SY
Hsieh
Tsu
T
Hsu
Cheng-Tai
CT
Lu
Chun-Hwa
CH
Chen
Ling-Hui
LH
Chou
Ching-Hui
CH
Chiu
Yun-I
YI
Chang
Ya-Ju
YJ
Tseng
Kuei-Rong
KR
Yen
Yu-Sheng
YS
Chao
Wen-Hsing
WH
Lin
Weir-Torn
WT
Jiaang
D000588:Amines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011720:Pyrazoles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors*
D000588:Amines; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; C031280:pyrazole; D051941:fms-Like Tyrosine Kinase 3