80240-40-0Relevant articles and documents
Design, Synthesis, and Biological Evaluation of Triazolone Derivatives as Potent PPARα/δDual Agonists for the Treatment of Nonalcoholic Steatohepatitis
Dai, Liang,Feng, Zhiqi,Li, Jiaxin,Liu, Hui,Liu, Junlong,Sun, Gang,Sun, Hongbin,Wen, Xiaoan,Xiang, Jiehao,Xu, Qinglong,Xu, Xiangrui,Yang, Shanlin,Yuan, Haoliang,Zhang, Shangran,Zheng, Runan
, p. 2571 - 2592 (2022/02/07)
Peroxisome proliferator-activator receptors α/δ(PPARα/δ) are regarded as potential therapeutic targets for nonalcoholic steatohepatitis (NASH). However, PPARα/δdual agonist GFT-505 exhibited poor anti-NASH effects in a phase III clinical trial, probably due to its weak PPARα/δagonistic activity and poor metabolic stability. Other reported PPARα/δdual agonists either exhibited limited potency or had unbalanced PPARα/δagonistic activity. Herein, we report a series of novel triazolone derivatives as PPARα/δdual agonists. Among them, compound H11 exhibited potent and well-balanced PPARα/δagonistic activity (PPARα EC50 = 7.0 nM; PPARδEC50 = 8.4 nM) and a high selectivity over PPARγ(PPARγEC50 = 1316.1 nM) in PPAR transactivation assays. The crystal structure of PPARδin complex with H11 revealed a unique PPARδ-agonist interaction. H11, which had excellent PK properties and a good safety profile, showed potent in vivo anti-NASH effects in preclinical models. Together, H11 holds a great promise for treating NASH or other inflammatory and fibrotic diseases.
3,3-DIFLUOROALLYLAMINES OR SALTS THEREOF AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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Paragraph 0232; 0235-0236, (2020/07/07)
The present technology provides 3,3-difluoroallylamines or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and uses thereof. The 3,3-difluoroallylamines or their pharmaceutically a
NOVEL ARYL OR HETEROARYL TRIAZOLONE DERIVATIVES OR SALTS THEREOF, OR PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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Paragraph 0166; 0171-0172; 0175-0176, (2019/10/15)
The present technology provides aryl or heteroaryl triazolone derivatives or pharmaceutically acceptable salts thereof, preparation processes thereof, pharmaceutical compositions comprising the same, and the use thereof. The aryl or heteroaryl triazolone derivatives or their pharmaceutically acceptable salts exhibit selective inhibitory activity on VAP-1 and therefore can be usefully applied, e.g., for the treatment and prophylaxis of nonalcoholic hepatosteatosis (NASH).
Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism
Sheng, Chunquan,Che, Xiaoying,Wang, Wenya,Wang, Shengzheng,Cao, Yongbing,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian
experimental part, p. 5276 - 5282 (2011/12/03)
The incidence of life-threatening fungal infections is increasing dramatically. In an attempt to develop novel antifungal agents, our previously synthesized phenoxyalkylpiperazine triazole derivatives were used as lead structures for further optimization. By means of structure-based bioisosterism, triazolone was used as a new bioisostere of oxygen atom. This type of bioisosteric replacement can improve the water solubility without loss of hydrogen-bonding interaction with the target enzyme. A series of triazolone-containing triazoles were rationally designed and synthesized. As compared with fluconazole, several compounds showed higher antifungal activity with broader spectrum, suggesting their potential for further evaluations.
Design, synthesis and antifungal evaluation of 1-(2-(2,4-difluorophenyl)-2- hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-1H-1,2,4-triazol-5(4H)-one
Jiang, Yongwei,Cao, Yongbin,Zhang, Jun,Zou, Yan,Chai, Xiaoyun,Hu, Honggang,Zhao, Qingjie,Wu, Qiuye,Zhang, Dazhi,Jiang, Yuanying,Sun, Qingyan
experimental part, p. 3135 - 3141 (2011/07/08)
Based on the structure of the active site of cytochrome P450 14α-demethylase (CYP51) and the conclusions of the structure-activity relationships of azole antifungals, a series of 1-(2-(2,4-difluoro-phenyl)-2- hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-1H-1,2,4-triazol-5(4H)-one of fluconazole analogs was synthesized. All compounds were characterized by IR, HRMS, 1HNMR and 13C NMR spectroscopic analysis. Results of preliminary antifungal in vitro test using eight human pathogenic species showed that some compounds displayed comparable or even better antifungal activities than reference drug fluconazole and that compound 3i exhibited significant activity against Candida albicans being worthy of further optimization.
Optically active antifungal azoles. VI. Synthesis and antifungal activity of N-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl) propyl]-N′-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones and 5(1H,4H)-tetrazolones
Kitazaki, Tomoyuki,Tamura, Norikazu,Tasaka, Akihiro,Matsushita, Yoshihiro,Hayashi, Ryogo,Okonogi, Kenji,Itoh, Katsumi
, p. 314 - 327 (2007/10/03)
A new series of optically active antifungal azoles, N-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl) propyl]-N′-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones (1,2) and 5(1H,4H)-tetrazolones (3), were prepared from the triflate derivative of (1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethanol (13) by an SN2 displacement reaction with the union of an azolone (17-19) and subsequent ring-opening reaction with 1H-1,2,4-triazole. The optically active oxiranylethanol 13 was synthesized from methyl (R)-lactate in a stereocontrolled manner. The azolones 1-3 prepared showed potent antifungal activities in vitro and in vivo.
