Quinazoline-based hydroxamic acid derivatives as dual histone methylation and deacetylation inhibitors for potential anticancer agents was written by Zheng, Haoting;Dai, Qiuzi;Yuan, Zigao;Fan, Tingting;Zhang, Cunlong;Liu, Zijian;Chu, Bizhu;Sun, Qinsheng;Chen, Yan;Jiang, Yuyang. And the article was included in Bioorganic & Medicinal Chemistry in 2022.Synthetic Route of C6H14N2 This article mentions the following:
In the present work, a series of quinazoline-based hydroxamic acid derivatives I (n = 5, 6; R = Me, i-Pr, Bn), II and III as dual GLP and HDAC inhibitors were designed and synthesized. These hybrid compounds I, II and III showed potent enzymic inhibitory activities against GLP and HDAC1/6 with IC50 values in the nanomolar range of less than 190 nM. Furthermore, most of the compounds displayed significant broad spectrum cytotoxic activities apart from I (n = 5; R = i-Pr) and III against all the tested cancer cells with IC50 values less than 50μM. Compounds I (n = 5; R = Me, n = 5; R = Bn) and II (R = Bn) (IV) showed more potent cytotoxic activities than I (n = 6; R = Me, n = 6; R = i-Pr) and II (R = i-Pr) in those cancer cells. Especially, compound IV showed potent inhibitory potency activity against both GLP and HDAC1/6 with IC50 values of 1.3, 89, 13 nM. Besides, IV exhibited the most potent antiproliferative activity against all the tested cancer cells. Further evaluations indicated that IV could inhibit the methylation and deacetylation of H3K9 on protein level. Moreover, IV could induce cancer cell apoptosis, G0/G1 cell cycle arrest, and partly block migration and invasion. All these thorough evaluations warranted IV as a promising lead compound worth further optimization and development for cancer therapy. 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 has a role as a reagent, a protic solvent, a base, a catalyst, a plant metabolite, a human metabolite and a non-polar solvent. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Synthetic Route of C6H14N2
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem