Synthesis and bioevaluation of 2-phenyl-4-methyl-1,3-selenazole-5-carboxylic acids as potent xanthine oxidase inhibitors

Guan, Qı; Cheng, Zengjin; Ma, Xiaoxue; Wang, Lijie; Feng, Dan; Cui, Yuanhang; Bao, Kai; Wu, Lan; Zhang, Weige

doi:10.1016/j.ejmech.2014.08.014

Cited by 60 publications

(28 citation statements)

References 18 publications

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“…Febuxostat and topiroxostat (Figure ) are both non‐purine XO inhibitors which possess excellent XO inhibitory activities and have been introduced into market in 2009 and 2013, respectively. Their approval greatly promoted the research of non‐purine XO inhibitors, and a number of compounds based on the scaffolds of febuxostat and topiroxostat have been recently reported such as Y‐700, isoxazoles, imidazoles, 1,2,3‐triazoles, selenazoles, 2‐(indol‐5‐yl)thiazoles, isocytosines, phenyl‐1,2,4‐triazoles, 4‐(pyridin‐4‐yl)‐1,2,3‐triazoles, and isonicotinamides…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and molecular docking studies of N‐(9,10‐anthraquinone‐2‐carbonyl)amino acid derivatives as xanthine oxidase inhibitors

Zhang

Wei

et al. 2018

Chem Biol Drug Des

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A series of N-(9,10-anthraquinone-2-carbonyl)amino acid derivatives (1a-j) was designed and synthesized as novel xanthine oxidase inhibitors. Among them, the L/D-phenylalanine derivatives (1d and 1i) and the L/D-tryptophan derivatives (1e and 1j) were effective with micromolar level potency. In particular, the L-phenylalanine derivative 1d (IC = 3.0 μm) and the D-phenylalanine derivative 1i (IC = 2.9 μm) presented the highest potency and were both more potent than the positive control allopurinol (IC = 8.1 μm). Preliminary SAR analysis pointed that an aromatic amino acid fragment, for example, phenylalanine or tryptophan, was essential for the inhibition; the D-amino acid derivative presented equal or greater potency compared to its L-enantiomer; and the 9,10-anthraquinone moiety was welcome for the inhibition. Molecular simulations provided rational binding models for compounds 1d and 1i in the xanthine oxidase active pocket. As a result, compounds 1d and 1i could be promising lead compounds for further investigation.

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Section: Introductionmentioning

confidence: 99%

Design, synthesis, and molecular docking studies of N‐(9,10‐anthraquinone‐2‐carbonyl)amino acid derivatives as xanthine oxidase inhibitors

Zhang

Wei

et al. 2018

Chem Biol Drug Des

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“…Therefore, identifying some novel non-purine XO inhibitors with potent XO inhibitory potency and fewer side effects is extremely necessary. In fact, some excellent non-purine XO inhibitors have been reported in the recent literature, including carboxyl moiety containing inhibitors, such as Febuxostat [5], Y-700 [6], selenazoles [7], isoxazoles [8] and 2-(indol-5-yl)thiazoles [9]; and non-carboxyl moiety containing inhibitors, like Topiroxostat [10], isocytosines [11e13], N-(1,3-diaryl-3-oxopropyl)amides [14], N-1-acetyl-3,5-diaryl-4,5-dihydro-(1H) pyrazoles [15], naphthoflavones [16], 2-amino-5-alkylidene-thiazol-4-ones [17], azaflavones [18], naphthopyrans [19], 4,6-diaryl/ heteroarylpyrimidin-2(1H)-ones [20], and 2,4-diaryl-pyrano [3,2-c] chromen-5(4H)-one [21] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of 1-hydroxy/methoxy-4-methyl-2-phenyl-1H-imidazole-5-carboxylic acid derivatives as non-purine xanthine oxidase inhibitors

Chen

Zhang

Wang

et al. 2015

European Journal of Medicinal Chemistry

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“…The need to retain the cyano group on the phenyl ring was confirmed by Guan et al. in their evaluation of 2‐aryl‐4‐methyl‐1,3‐selenazole‐5‐carboxylic acids 126 as XO inhibitors . All the compounds obtained with different substituents in the R 1 position and a nitro group as R 2 consistently exhibited lower activity than the corresponding structures with a cyano group in place of the nitro group.…”

Section: Non‐purine‐like Inhibitors Of Xomentioning

confidence: 99%

Inhibitors of Xanthine Oxidase: Scaffold Diversity and Structure‐Based Drug Design

2019

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Xanthine oxidase (XO) is the enzyme responsible for the catabolism of purines and their conversion into uric acid. XO is thus the target for the treatment of hyperuricemia and gout. For more than 50 years the only XO inhibitor drug available on the market was the purine analogue allopurinol. In the last decade there has been a resurgence in the search for new inhibitors of XO, as the activity of XO and hyperuricemia have also been associated with a variety of conditions such as diabetes, hypertension, and other cardiovascular diseases. In recent years the non‐purine inhibitor febuxostat was approved in Europe and the USA for the treatment of hyperuricemia. This drug was followed by another XO inhibitor called topiroxostat. This review discusses the molecular structures and activities of the multiple classes of inhibitors that have been developed since the discovery of allopurinol, with a brief review of the molecular interactions between inhibitors and XO active site residues for the most important molecules. The challenges ahead for the discovery of new inhibitors of XO with novel chemical structures are discussed.

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Synthesis and bioevaluation of 2-phenyl-4-methyl-1,3-selenazole-5-carboxylic acids as potent xanthine oxidase inhibitors

Cited by 60 publications

References 18 publications

Design, synthesis, and molecular docking studies of N‐(9,10‐anthraquinone‐2‐carbonyl)amino acid derivatives as xanthine oxidase inhibitors

Design, synthesis, and molecular docking studies of N‐(9,10‐anthraquinone‐2‐carbonyl)amino acid derivatives as xanthine oxidase inhibitors

Synthesis and evaluation of 1-hydroxy/methoxy-4-methyl-2-phenyl-1H-imidazole-5-carboxylic acid derivatives as non-purine xanthine oxidase inhibitors

Inhibitors of Xanthine Oxidase: Scaffold Diversity and Structure‐Based Drug Design

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