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

Chen, Shaolei; Zhang, Tingjian; Wang, Jian; Wang, Fangyang; Niu, Handong; Wu, Chunfu; Wang, Shao-Jie

doi:10.1016/j.ejmech.2015.08.056

Cited by 68 publications

(37 citation statements)

References 29 publications

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“…Of the synthesized (64-66) showed good XO inhibitory activity with IC 50 values of 0.003, 0.003, and 0.006 M, respectively. Lineweaver-Burk plot analysis also showed that 66 acted as mixed-type inhibitor of XO 145. Bhawna and team synthesized a series ofF I G U R E 1 1 Thiazolidinedione (42-45) and carinol derivatives (46-48) as XO inhibitors Interactions of indole-3-acetaldehyde 49 (A) and guanine 50 (B) at the binding site of XO F I G U R E 1 Phenol derivatives (51-52) as XO inhibitors 5-substituted imidazolones as the potent inhibitors of XO; 4-(2-chlorobenzylidene)-1-(3-chloro-4-fluorophenyl)-2-phenyl-1H-imidazol-5(4H)-one (67) was shown to be the most potent inhibitor versus allopurinol (IC 50 6 vs. 11.10 M).…”

mentioning

confidence: 88%

“…Of the synthesized ( 64–66 ) showed good XO inhibitory activity with IC 50 values of 0.003, 0.003, and 0.006 μM, respectively. Lineweaver–Burk plot analysis also showed that 66 acted as mixed‐type inhibitor of XO . Bhawna and team synthesized a series of 5‐substituted imidazolones as the potent inhibitors of XO; 4‐(2‐chlorobenzylidene)‐1‐(3‐chloro‐4‐fluorophenyl)‐2‐phenyl‐1 H ‐imidazol‐5(4H)‐one ( 67 ) was shown to be the most potent inhibitor versus allopurinol (IC 50 6 vs. 11.10 μM) .…”

Section: Xanthine Oxidasementioning

confidence: 99%

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Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

Kumar

Joshi

Kler

et al. 2017

Medicinal Research Reviews

101

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Almost all drug molecules become the substrates for oxidoreductase enzymes, get metabolized into more hydrophilic products and eliminated from the body. These metabolites sometime may be more potent, active, inactive, or toxic in nature compared to parent molecule. Xanthine oxidoreductase and aldehyde oxidase belong to molybdenum containing family and are well characterized for their structures and functions, in particular to their ability to oxidize/hydroxylate the xenobiotics. Their upregulated clinical levels causing oxidative stress are associated with pathways either directly involved in the progression of diseases, gout, or indirectly with the succession of other diseases such as diabetes, cancer, etc. Herein, we have put forth a comprehensive review on the xanthine and aldehyde oxidases pertaining to their structures, functions, pathophysiological role, and a comparative analysis of structural insights of xanthine and aldehyde oxidases' binding domains with endogenous ligands or inhibitors. Though both the enzymes are molybdenum containing and are likely to share some common pathways and interact with inhibitors in a similar manner but we have focused on structural prerequisites for inhibitor specificity to both the enzymes keeping in view of the existing X-ray structures. This review also provides futuristic implications in the design of inhibitors derived from inorganic complexes or small organic molecules considering the spatial features and structural insights of both the enzymes.

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mentioning

confidence: 88%

Section: Xanthine Oxidasementioning

confidence: 99%

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

Kumar

Joshi

Kler

et al. 2017

Medicinal Research Reviews

101

View full text Add to dashboard Cite

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“…Imidazole derivativesm aintaining similarities with febuxostat were synthesized by Chen et al and reported in 2015. [94] Several compounds for the two series of analogueso f1 -hydroxyand 1-methoxy-substituted 2-aryl-4-methyl-1H-imidazole-5-carboxylic acids 110 and 111 were tested in vitro as XO inhibitors. The derivatives with af ree hydroxy group at position 1o ft he imidazole ring demonstrated better activity than derivatives with am ethoxy group at the same position.…”

Section: Febuxostat and Topiroxostat Analoguesmentioning

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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“…6 Given these limitations, research has focused on the development of novel non-purine XO inhibitors with potent XO inhibitory potency, but with fewer side effects. In recent decades, a great amount of non-purine XO inhibitors of various chemotypes have been reported, such as Febuxostat (approved in USA, 2009), 7 Y-700, 8 Topiroxostat (approved in Japan, 2013), 9 isoxazoles, 10 schiff bases of benzaldehydes, 11 N-(1,3-diaryl-3-oxo-propyl)amides, 12 N-acetyl pyrazolines, 13 isocytosines, 14 selenazoles, 15 imidazoles, 16 2-(indol-5-yl)thiazoles, 17 chalcones, 18 and 9-deazaguanines. 19 In our previous studies on anthraquinone compounds as anti-tumor agents, we unexpectedly found a compound (1a), which contained a benzaldehyde moiety and an anthraquinone moiety linked by a 1,2,3-triazole ( Fig.…”

mentioning

confidence: 99%

“…The testing method has been described in our previous study. 16 Allopurinol was included as a reference compound.…”

mentioning

confidence: 99%

Discovery and biological evaluation of some (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety as potent xanthine oxidase inhibitors

Zhang

Wei

et al. 2017

Bioorganic & Medicinal Chemistry Letters

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A series of (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety were synthesized and identified as novel xanthine oxidase inhibitors. Among them, the most promising compounds 1h and 1k were obtained with IC values of 0.6μM and 0.8μM, respectively, which were more than 10-fold potent compared with allopurinol. The Lineweaver-Burk plot revealed that compound 1h acted as a mixed-type xanthine oxidase inhibitor. SAR analysis showed that the benzaldehyde moiety played a more important role than the anthraquinone moiety for inhibition potency. The basis of significant inhibition of xanthine oxidase by 1h was rationalized by molecular modeling studies.

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

Cited by 68 publications

References 29 publications

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

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

Discovery and biological evaluation of some (1H-1,2,3-triazol-4-yl)methoxybenzaldehyde derivatives containing an anthraquinone moiety as potent xanthine oxidase inhibitors

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