13724-18-0Relevant academic research and scientific papers
Design, synthesis and biological evaluation of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives as novel xanthine oxidase inhibitors
Zhang, Ting-jian,Li, Song-ye,Wang, Lin,Sun, Qi,Wu, Qing-xia,Zhang, Yi,Meng, Fan-hao
, p. 362 - 372 (2017)
A series of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives was designed, synthesized and evaluated for inhibitory potency in vitro against xanthine oxidase. The isonicotinamide series was considerably more effective than the nicotinamide series. SARs analysis revealed that the isonicotinoyl moiety played a significant role on the inhibition and that a benzyl ether tail (e.g., ortho-cyanobenzoxy) linked to the benzonitrile moiety benefits the inhibitory potency. Among these compounds, 10q (IC50 = 0.3 μM) was identified to be the most potent in this work and was observed to be 28.3-fold more potent than allopurinol but 20-fold less potent than topiroxostat. The Lineweaver-Burk plot showed that 10q acted as a mixed-type inhibitor on xanthine oxidase. Molecular modeling provided a reasonable explanation for the SARs observed in this study.
Synthesis and evaluation of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives as xanthine oxidase inhibitors
Zhang, Ting-jian,Wu, Qing-xia,Li, Song-ye,Wang, Lin,Sun, Qi,Zhang, Yi,Meng, Fan-hao,Gao, Hua
, p. 3812 - 3816 (2017/07/27)
This study mainly focused on the modification of the X2 position in febuxostat analogs. A series of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives (1a-s) with an N atom occupying the X2 position was designed and synthesized. Evaluation of their inhibitory potency in vitro on xanthine oxidase indicated that these compounds exhibited micromolar level potencies, with IC50 values ranging from 0.21?μM to 26.13?μM. Among them, compound 1s (IC50?=?0.21?μM) showed the most promising inhibitory effects and was 36-fold more potent than allopurinol, but was still 13-fold less potent than the lead compound Y-700, which meant that a polar atom fused at the X2 position could be unfavorable for potency. The Lineweaver-Burk plot revealed that compound 1s acted as a mixed-type xanthine oxidase inhibitor. Analysis of the structure-activity relationships demonstrated that a more lipophilic ether tail (e.g., meta-methoxybenzoxy) at the 4′-position could benefit the inhibitory potency. Molecular modeling provided a reasonable explanation for the structure–activity relationships observed in this study.
N-(3-cyano-4-alkoxyphenyl) pyridine carboxamide compound and application thereof
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Paragraph 0075-0080; 0101-0102, (2017/08/09)
The invention belongs to the field of medicines, and particularly relates to an N-(3-cyano-4-alkoxyphenyl) pyridine carboxamide compound and application thereof. The N-(3-cyano-4-alkoxyphenyl) pyridine carboxamide compound disclosed by the invention refle
1-substituted phenyl-1H-1,2,3-triazole compound as well as preparation method and application thereof
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Paragraph 0018; 0029, (2016/11/17)
The invention relates to a 1-substituted phenyl-1H-1,2,3-triazole compound, in particular to a compound applicable to preparation of anti-gout drugs and a preparation method of the compound, and belongs to the field of medicines. The compound is as shown in the general formula, wherein each R1 is independent alkyl of 1-10 carbons, 3-10 carbon atom naphthenic bases, allyl, methoxy ethyl, benzyl and substituted benzyl; substituted benzyl can be p-halogenated benzyl, p-cyano benzyl and p-alkoxy benzyl; each R2 is independent H or methyl; each R3 is independent H or ethyl. Experimental results show that the compound has a good effect in the in-vitro xanthine oxidase inhibition activity test.
