Zhu, Huajian; Li, Wenlong; Shuai, Wen; Liu, Yang; Yang, Limei; Tan, Yuchen; Zheng, Tiandong; Yao, Hong; Xu, Jinyi; Zhu, Zheying; Yang, Dong-Hua; Chen, Zhe-Sheng; Xu, Shengtao published the artcile< Discovery of novel N-benzylbenzamide derivatives as tubulin polymerization inhibitors with potent antitumor activities>, Formula: C6H8N2, the main research area is colchicine binding antitumor safety profile; benzylbenzamide preparation cytotoxicity antitumor mol docking tubulin inhibitor; Anti-vascular; Antitumor; Druggability; N-benzylbenzamide; Tubulin inhibitors.
A series of novel N-benzylbenzamide derivatives I (R = dimethylaminyl, piperidin-1-yl, morpholin-4-yl, etc.; R1 = H, Cl, NO2, (pyridin-4-ylmethyl)aminyl, etc.; R2 = H, NO2; R3 = (3-hydroxy-4-methoxyphenyl)methyl, (3-fluoro-4-methoxyphenyl)methyl, pyridin-4-ylmethyl, etc.; R4 = H, Me), II (X = Y = N, CH) and III were designed and synthesized as tubulin polymerization inhibitors. Among fifty-one target compounds, I, II and III compound I [R = morpholin-4-yl; R1 = F; R2 = H; R3 = (3-hydroxy-4-methoxyphenyl)methyl; R4 = H] (IV) exhibited significant antiproliferative activities with IC50 values ranging from 12 to 27 nM against several cancer cell lines, and possessed good plasma stability and satisfactory physicochem. properties. Mechanism studies demonstrated that IV bound to the colchicine binding site and displayed potent anti-vascular activity. Notably, the corresponding disodium phosphate III exhibited an excellent safety profile with the LD50 value of 599.7 mg/kg (i.v. injection), meanwhile, it significantly inhibited tumor growth and decreased microvessel d. in liver cancer cell H22 allograft mouse model without obvious toxicity. Collectively, IV and III are novel promising anti-tubulin agents with more druggable properties and deserve to be further investigated for cancer therapy.
European Journal of Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 3731-53-1 belongs to class pyridine-derivatives, and the molecular formula is C6H8N2, Formula: C6H8N2.