1008-30-6Relevant 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.
Dammarane sapogenin derivative and preparation method and application thereof
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Paragraph 0087; 0249-0251, (2020/10/04)
The invention belongs to the technical field of medicines, and relates to a dammarane sapogenin derivative and a preparation method and application thereof. A series of dammarane sapogenin derivativesare obtained by combining dammarane sapogenins from plants with different groups. Anticancer activity evaluation and anticancer activity mechanism research are carried out on the derivative, and results show that the prepared dammarane sapogenin derivative has a remarkable anticancer effect, has no toxic effect on normal cells and can be used for preparing drugs for treating cancers.
Design, synthesis, evaluation, and molecular docking of ursolic acid derivatives containing a nitrogen heterocycle as anti-inflammatory agents
Wei, Zhi-Yu,Chi, Ke-Qiang,Wang, Ke-Si,Wu, Jie,Liu, Li-Ping,Piao, Hu-Ri
, p. 1797 - 1803 (2018/04/23)
Ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were synthesized in an attempt to develop potent anti-inflammatory agents. Structures of the synthesized compounds were elucidated by 1H NMR, 13C NMR, and HRMS. Most of the synthesized compounds showed pronounced anti-inflammatory effects at 100 mg/kg. In particular, compound 11b, which displayed the most potent anti-inflammatory activity of all of the compounds prepared, with 69.76% inhibition after intraperitoneal administration, was more potent than the reference drugs indomethacin and ibuprofen. The cytotoxicity of the compounds was also assessed by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and no compounds showed any appreciable cytotoxic activity (IC50 >100 μmol/L). Furthermore, molecular docking studies of the synthesized compounds were performed to rationalize the obtained biological results. Overall, the results indicate that compound 11b could be a therapeutic candidate for the treatment of inflammation.
Design, synthesis, and negative inotropic evaluation of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties
Wei, Zhi-Yu,Cui, Bai-Ri,Cui, Xun,Wu, Yan-Ling,Fu, Yang,Liu, Li-Ping,Piao, Hu-Ri
, p. 47 - 60 (2016/12/16)
In this study, four novel series of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties were designed, synthesized, and evaluated for negative inotropic activity by measuring the left atrium stroke volume in isolated rabbit heart preparations. Almost all of the compounds showed an ability to moderate the cardiac workload by decreasing the heart rate and contractility. Among them, 7h was found to be the most potent with a change in stroke volume of ?48.22?±?0.36% at a concentration of 3?×?10?5?mol/L (metoprolol: ?9.74?±?0.14%). The cytotoxicity of these compounds was evaluated using the human cervical cancer cell line HeLa, the liver cancer cell line Hep3B, and the human normal hepatic cell line LO2. A preliminary study of the mechanism of action for the compound 7h on the regulation of atrial dynamics with ATP-sensitive K+ channel and L-type Ca2+ channel blockers glibenclamide and nifedipine was performed in the isolated perfused beating rabbit atria.
First N-Heterocyclic Carbenes Relying on the Triazolone Structural Motif: Syntheses, Modifications and Reactivity
Jonek, Markus,Diekmann, Janina,Ganter, Christian
, p. 15759 - 15768 (2015/11/03)
4-Phenylsemicarbazide and 1,5-diphenylcarbazide are suitable starting materials for the syntheses of N-heterocyclic carbene (NHC) compounds with new backbone structures. In the first case, cyclisation and subsequent methylation leads to a cationic precurs
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.
Microwave-assisted N-debenzylation of amides with triflic acid
Rombouts, Frederik,Franken, Dennis,Martínez-Lamenca, Carolina,Braeken, Mirielle,Zavattaro, Chiara,Chen, Jinsheng,Trabanco, Andrés A.
experimental part, p. 4815 - 4818 (2010/10/02)
A new and facile microwave-assisted protocol for the debenzylation of N-benzylamides with triflic acid has been developed. Both secondary and tertiary aliphatic or aromatic amides are obtained in moderate to good yields.
Synthesis of amides of 2,4-dioxothiazolidin-5-yl acetic acid with 1,2,4-triazole substituents
Trotsko, Nazar,Dobosz, Maria,Chodkowska, Anna,Jagiello-Wojtowicz, Ewa
body text, p. 217 - 221 (2009/04/04)
In the reaction of (2,4-dioxothiazolidin-5-yl)acetyl chloride with 1,2,4-triazole, 4-phenyl-1,2,4-triazolin-5-one and 4-phenyl-1,2,4-triazolin-5- thione, the new corresponding amides (2-4) were obtained. For compounds 2 and 4 effects on central nervous system (CNS) of mice were studied.
