14213-13-9Relevant articles and documents
Design and biological evaluation of tetrahydropyridine derivatives as novel human GPR119 agonists
Zuo, Zeping,Chen, Miaomiao,Shao, Xiaoni,Qian, Xinying,Liu, Xiaocong,Zhou, Xia,Xiang, Jiawei,Deng, Pengchi,Li, Yan,Jie, Hui,Liu, Chunqi,Cen, Xiaobo,Xie, Yongmei,Zhao, Yinglan
supporting information, (2020/01/08)
A series of novel tetrahydropyridine derivatives were prepared and evaluated using cell-based measurements. Systematic optimization of general structure G-1 led to the identification of compound 35 (EC50 = 4.9 nM) and 37 (EC50 = 8.8 nM) with high GPR119 agonism activity and moderate clog P. Through single and long-term pharmacodynamic experiments, we found that compound 35 showed a hypoglycemic effect and may have an effect on improving basal metabolic rate in DIO mice. Both in vitro and in vivo tests indicated that compound 35 was a potential potent GPR119 agonist in allusion to T2DM treatment.
Synthesis and transformations of 1-(azidophenyl)-1H-tetrazoles
Pokhodylo,Matiichuk,Obushak
scheme or table, p. 556 - 560 (2010/08/20)
Diazotization of 1-(aminophenyl)-1H-tetrazoles and subsequent treatment of the diazonium salts with sodium azide gave 1-(azidophenyl)-1H-tetrazoles which were brought into cyclization with ethyl acetoacetate and cyanoacetanilide to obtain 1,2,3-triazole derivatives. Under these conditions, the tetrazole ring may undergo cleavage with formation of cyanamide group.
Optically active antifungal azoles. XI. An alternative synthetic route for 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl )propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (TAK-456) and its analog
Ichikawa, Takashi,Kitazaki, Tomoyuki,Matsushita, Yoshihiro,Hosono, Hiroshi,Yamada, Masami,Mizuno, Masahiro,Itoh, Katsumi
, p. 1947 - 1953 (2007/10/03)
New routes for the synthesis of the optically active antifungal triazoles 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-Hydroxy-1-Methyl-3-(1H-1,2,4-triazol-1-Yl )propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1b) and the 3-[4-(1H-1,2,3-triazol-1-Yl)phenyl]-2-imidazolidinone analog (1a) that possess an imidazolidine nucleus were established. The key synthetic intermediates, (2R,3R)-3-(2,2-diethoxyethyl)amino-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol -1-Yl)-2-butanol (8) and (2R,3R)-2-(2,4-difluorophenyl)-3-(2-hydroxyethyl)amino-1-(1H-1,2,4-triazol-1- yl)-2-butanol (14), were prepared by the ring-Opening reaction of the oxirane (2) with the corresponding 2-Substituted ethylamines. The acetal (8) was converted to the imidazolidinones (1a, b) by condensation with the carbamates (10a, b) followed by treatment with hydrochloric acid and subsequent catalytic hydrogenation. The candidate selected for the clinical trials, 1b (TAK-456), was alternatively prepared from the hydroxyethylamino intermediate (14) via two reaction steps: condensation with the carbamate (10b) to the urea (15) and subsequent cyclization to the imidazolidinones. This newly developed synthetic route could be applied to a large scale preparation of 1b.