Category: bromides-buliding-blocksIn 2021 ,《Design, synthesis, biological evaluation and pharmacophore model analysis of novel tetrahydropyrrolo[3,4-c]pyrazol derivatives as potential TRKs inhibitors》 was published in European Journal of Medicinal Chemistry. The article was written by Wu, Tianxiao; Zhang, Chu; Lv, Ruicheng; Qin, Qiaohua; Liu, Nian; Yin, Wenbo; Wang, Ruifeng; Sun, Yin; Wang, Xiaoyan; Sun, Yixiang; Zhao, Dongmei; Cheng, Maosheng. The article contains the following contents:
Synthesis, biol. evaluation and pharmacophore model anal. of novel tetrahydropyrrolo[3,4-c]pyrazol derivatives I [Ar1 = Ph, 2-FC6H4, 3-ClC6H4, etc.] and II [R1 = H, F; R2 = H, F; Ar2 = 4-FC6H4, 2-naphthyl, 4-morpholinophenyl, etc.] as potential TRKs inhibitors were obtained using scaffold hopping strategy. Compound II [R1 = H; R2 = F; Ar2 = 4-(4-methylpiperazin-1-yl)-phenyl] significantly inhibited the proliferation of TRK-dependent cell lines (Km-12), while it had no inhibitory effect on TRK-independent cell lines (A549 and THLE-2). Furthermore, kinases selectivity profiling showed that in addition to TRKs, compound II [R1 = H; R2 = F; Ar2 = 4-(4-methylpiperazin-1-yl)-phenyl] only displayed relatively strong inhibitory activity on ALK. These data might indicated that compound II [R1 = H; R2 = F; Ar2 = 4-(4-methylpiperazin-1-yl)-phenyl] had a good drug safety. Partial ADME properties were evaluated in vitro and in vivo and compound II [R1 = H; R2 = F; Ar2 = 4-(4-methylpiperazin-1-yl)-phenyl] exhibited a good AUC values and volume of distribution and low clearance in the pharmacokinetics experiment of rats. In the experiment, the researchers used many compounds, for example, 4-Bromobenzoic acid(cas: 586-76-5Category: bromides-buliding-blocks)
4-Bromobenzoic acid(cas: 586-76-5) has been used to study the metabolic fate of 2-,3-and 4-bromo benzoic acids in rat hepatocytes incubation using high temperature liquid chromatography. It was used in bromine-specific detection of the metabolites of 2-,3-and 4-bromobenzoic acid in the urine and bile of rats by inductively coupled plasma mass spectrometry.Category: bromides-buliding-blocks
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary