Discovery of Potent and Orally Effective Dual Janus Kinase 2/FLT3 Inhibitors for the Treatment of Acute Myelogenous Leukemia and Myeloproliferative Neoplasms was written by Yang, Tao;Hu, Mengshi;Qi, Wenyan;Yang, Zhuang;Tang, Minghai;He, Jun;Chen, Yong;Bai, Peng;Yuan, Xue;Zhang, Chufeng;Liu, Kongjun;Lu, Yulin;Xiang, Mingli;Chen, Lijuan. And the article was included in Journal of Medicinal Chemistry in 2019.Safety of tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate This article mentions the following:
Herein, the design, synthesis, and structure-activity relationships of a series of unique 4-(1H-pyrazol-4-yl)-pyrimidin-2-amine derivatives that selectively inhibit Janus kinase 2 (JAK2) and FLT3 kinases is described. These screening cascades revealed that I was a preferred compound with IC50 values of 0.7 and 4 nM for JAK2 and FLT3, resp. Moreover, I was a potent JAK2 inhibitor with 37-fold and 56-fold selectivity over JAK1 and JAK3, resp., and possessed an excellent selectivity profile over the other 100 representative kinases. In a series of cytokine-stimulated cell-based assays, I exhibited a higher JAK2 selectivity over other JAK isoforms. The oral administration of 60 mg/kg of I could significantly inhibit tumor growth, with a tumor growth inhibition rate of 93 and 85% in MV4-11 and SET-2 xenograft models, resp. Addnl., I showed an excellent bioavailability (F = 58%), a suitable half-life time (T1/2 = 4.1 h), a satisfactory metabolic stability, and a weak CYP3A4 inhibitory activity, suggesting that I might be a potential drug candidate for JAK2-driven myeloproliferative neoplasms and FLT3-internal tandem duplication-driven acute myelogenous leukemia. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate (cas: 154590-34-8Safety of tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate).
tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate (cas: 154590-34-8) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Safety of tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics