当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis and biological evaluation of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives as novel xanthine oxidase inhibitors.

Design, synthesis and biological evaluation of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives as novel xanthine oxidase inhibitors.

Abstract：

: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.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Zhang TJ,Li SY,Wang L,Sun Q,Wu QX,Zhang Y,Meng FH

doi

10.1016/j.ejmech.2017.09.051

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

362-372

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(17)30766-3

journal_volume

141

pub_type

杂志文章

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