A patent update on therapeutic applications of urease inhibitors (2012–2018)

ABSTRACT

Introduction: Urease is a nickel-containing metalloenzyme that is commonly found in different bacteria, plants, algae, and fungi and mediates the growth of many pathogenic bacteria in the acidic environment of the stomach. Despite the large number of molecules known to have excellent urease inhibitory activity, there is an alarming lack of urease inhibitor drugs on the market.

Area covered: This review aims to provide a comprehensive overview of the different types of molecules patented as potent urease inhibitors from the year 2012 to 2018.

Expert opinion: Urease is an important target to treat urease-related bacterial infections manifesting as gastric ulcers, urinary tract infections, and kidney stones. Although many different molecules as inhibitors of urease have been reported, only a few have advanced to clinical trials. The development of new effective urease inhibitors demands new suitable lead molecules. This review covers the patents on urease inhibitors in recent years (2012–2018) with a hope to bring into focus the issue and need for availability of new urease inhibitors on the market.

KEYWORDS:

• Urease
• urease inhibitors
• antibacterial activity
• H. pylori infections

Article highlights

• Urease is a nickel-containing metalloenzyme that is responsible for the virulence of many pathogenic bacteria, including the H. pylori.

• The bacterium H. pylori is able to evade the harsh acidic environment of the stomach and can, therefore, expand its colonies, making the infection that much more difficult to treat with traditional antibiotics. The urease enzyme is able to do so by virtue of its ability to catalyze the conversion of urea into ammonia, thereby allowing the bacterial colonies to thrive.

• The only commercially available urease inhibitor drug Lithostat (acetohydroxamic acid) is often prescribed along with traditional antibiotics to counter the bacterial infection; however, many adverse reactions are associated with the use of Lithostat. Hence, there is an urgent need for new urease inhibiting drugs.

• Herein, we have reviewed different molecules patented as urease inhibitors, from 2012 to 2018.

Acknowledgments

H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, and Higher Education Commission (HEC) Pakistan [Project No. 4732/5743] are gratefully acknowledged for their financial support.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper received funding from Higher Education Commission (HEC) project grant no. 4732/5743.