Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model was written by Heng, Hao;Wang, Zhijie;Li, Hongmei;Huang, Yatian;Lan, Qingyuan;Guo, Xiaoxing;Zhang, Liang;Zhi, Yanle;Cai, Jiongheng;Qin, Tianren;Xiang, Li;Wang, Shuxian;Chen, Yadong;Lu, Tao;Lu, Shuai. And the article was included in European Journal of Medicinal Chemistry in 2019.Synthetic Route of C6H14N2 This article mentions the following:
FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and down regulation of P-STAT5 were also observed in tumor cells extracted from the MV4-11 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML. In the experiment, the researchers used many compounds, for example, 4-Amino-1-methylpiperidine (cas: 41838-46-4Synthetic Route of C6H14N2).
4-Amino-1-methylpiperidine (cas: 41838-46-4) belongs to piperidine derivatives.Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Several piperidine alkaloids isolated from natural herbs, were found to exhibit antiproliferation and antimetastatic effects on various types of cancers both in vitro and in vivo for example Piperine, Evodiamine, Matrine, Berberine and Tetrandine.Synthetic Route of C6H14N2
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem