The author of 《Discovery of novel mutant-combating ALK and ROS1 dual inhibitors bearing imidazolidin-2-one moiety with reasonable PK properties》 were Lei, Hongrui; Jiang, Nan; Miao, Xiuqi; Xing, Lingyun; Guo, Ming; Liu, Yang; Xu, Haowen; Gong, Ping; Zuo, Daiying; Zhai, Xin. And the article was published in European Journal of Medicinal Chemistry in 2019. Reference of 1-Methylpiperazine The author mentioned the following in the article:
Aiming to identify novel potent ALK and ROS1 dual inhibitors, the relatively bulky piperidine fragment in ceritinib was replaced with substituted imidazolidin-2-one moiety which gave rise to a series of 2,4-diaryl-aminopyrimidine (DAAP) analogs. SAR studies were conducted based on cellular assays on five cell lines and most compounds exerted moderated to excellent activities. Among them, 15(I) showed excellent inhibitory activities against ROS1 and ALK pos. cell lines, especially Ba/F3G1202R, with IC50 values ranging from 14 to 37 nM. As a continuation, several compounds were tested in enzymic assays and I displayed encouraging activities against wild-type ALK (1.2 nM), ROS1(0.43 nM) as well as extremely resistant ALKL1196M and ALKG1202R mutants with IC50 values of 0.73 nM and 6.7 nM, resp. To our delight, both cellular and enzymic results of I were in good accordance with western blot assays on H2228 and HCC78 cell lines. Importantly, pharmacokinetic (PK) profiles of I were obtained with quite satisfying AUC and Cmax values. Besides, the binding models of I with ALKWT, ALKG1202R and ROS1 clearly present the essential interactions within the active site. The experimental part of the paper was very detailed, including the reaction process of 1-Methylpiperazine(cas: 109-01-3Reference of 1-Methylpiperazine)
1-Methylpiperazine(cas: 109-01-3) can be used as mimic template in the preparation of molecularly imprinted microspheres (MIMs). It was also used to prepare the difunctional strong anion-exchange stationary phase from a 1,4-diazacyclohexane derivative..Reference of 1-Methylpiperazine
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics