Discovery of (E)-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-((3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thio)propanamide (CHMFL-ABL-121) as a highly potent ABL kinase inhibitor capable of overcoming a variety of ABL mutants including T315I for chronic myeloid leukemia was written by Liu, Xuesong;Wang, Beilei;Chen, Cheng;Jiang, Zongru;Hu, Chen;Wu, Hong;Zhang, Yicong;Liu, Xiaochuan;Wang, Wenliang;Wang, Junjie;Hu, Zhenquan;Wang, Aoli;Huang, Tao;Liu, Qingwang;Wang, Wei;Wang, Li;Wang, Wenchao;Ren, Tao;Li, Lili;Xia, Ruixiang;Ge, Jian;Liu, Qingsong;Liu, Jing. And the article was included in European Journal of Medicinal Chemistry in 2018.Product Details of 630125-91-6 This article mentions the following:
There is still a great demand in the clinic for the drugs which can overcome a variety of imatinib resistant ABL mutants. Starting from a type I inhibitor axitinib, which has been reported to overcome ABL-T315I mutant induced resistance, through a structure guided drug design approach and binding mode switch strategy, the authors have discovered a novel type II ABL inhibitor I (CHMFL-ABL-121), which significantly improved the inhibitory activity against ABL wt and a broad spectrum of mutants including the most prevalent imatinib-resistant gatekeeper mutant T315I. I exhibited IC50 values of 2 nM and 0.2 nM against purified inactive ABL wt and T315I kinase protein resp. and inhibited the proliferation of the established CML cell lines with GI50 at single digit nM. In cellular context, I strongly affected BCR-ABL mediated signaling pathways and induced apoptosis as well as arrested cell cycle at G0/G1 phase. In the in vivo study, 50 mg/kg/day dosage of I displayed TGI of 52% in the TEL-ABLT315I-BaF3 cell inoculated allograft mouse model without obvious toxicity. In the experiment, the researchers used many compounds, for example, 4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6Product Details of 630125-91-6).
4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (cas: 630125-91-6) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Product Details of 630125-91-6
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Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics