An updated patent review: xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015)

ABSTRACT

Introduction: Xanthine oxidase (XO) is a versatile molybdoflavoprotein, widely distributed, occurring in milk, kidney, lung, heart, and vascular endothelium. Catalysis by XO to produce uric acid and reactive oxygen species leads to many diseases. Anti hyperuricemic therapy by xanthine oxidase inhibitors has been mainly employed for the treatment of gout.

Area covered: This review covers the patent literature (2011–2015) and also presents the interesting strategies/rational approaches employed for the design of xanthine oxidase inhibitors reported recently.

Expert opinion: Recent literature indicates that various non purine scaffolds have been extensively investigated for xanthine oxidase inhibition. The significant potential endowed by heteroaryl based compounds, in particularly fused heterocycles clearly highlights their clinical promise and the need for detailed investigation. Studies by various research groups have also revealed that the flavone framework is open for isosteric replacements and structural modifications for yielding potent non purine xanthine oxidase inhibitors. In addition, various plant extracts recently reported to possess significant xanthine oxidase inhibitory potential presents enough promise to initiate a screening program for the identification of other plant extracts and phytoconstituents possessing inhibitory potential towards the enzyme.

KEYWORDS:

• Xanthine oxidase inhibitors
• allopurinol
• febuxostat
• gout
• purine
• non purine

Article highlights

• Focus on the design and synthesis of non-purine xanthine oxidase inhibitors continues to be an area of interest

• Plant extracts and the phytoconstituents isolated from them have displayed significant xanthine oxidase inhibitory potential

• The technique of molecular hybridization has shown promise for the design of non purine xanthine oxidase inhibitors

• Indole based non purine inhibitors have exhibited remarkable activity at nanomolar levels

• Flavone scaffold has been explored further for xanthine oxidase inhibition

• Molecular modeling studies have played a key role in the rationalization of results of in vitro and in vivo xanthine oxidase inhibitory assays of designed agents.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Funding

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