Inhibitory activities of bipyrazoles: a patent review

ABSTRACT

Introduction

Bipyrazole is constituted from two pyrazole units either in their fully aromatic or partially hydrogenated forms. Pyrazoles are widely available in pharmaceutical and agrochemical products. Some pyrazoles are essential parts of commercial drugs in the market. This inspired us to collect the pharmacological activities of bipyrazoles that have potential therapeutic behaviors in several biological aspects but none of them were included in commercial drugs.

Areas covered

This review covers all biological and pharmacological potentials of bipyrazole derivatives during 2010–2021. The topics of this review comprised anticancer, antioxidant, anti-inflammatory, antimicrobial, antitubercular, antimalarial, insecticidal activities as well as enzymatic inhibitions.

Expert opinion

Bipyrazoles demonstrated a wide array of potent activities against various diseases such as anticancer, antitubercular, anti-inflammatory, and antimicrobial activities. Those are of great benefits for medicinal researchers to develop promising building blocks of bipyrazoles for treatment of diseases. The SAR studies showed that metallated bipyrazoles had better biological activities than bipyrazole ligands. For example, gold(III) and iridium(II) complexes of bipyrazoles were proved to be anticancer agents, and copper(I) as well as silver(I) complexes had excellent antibacterial activities. Several bipyrazoles were reported as antimalarial inhibitors better than chloroquine, the possible COVID-19 drug.

KEYWORDS:

• anticancer
• antitubercular
• antimicrobial
• anti-inflammatory
• bipyrazoles
• enzymes inhibitors
• pyrazoles
• pyrazolines

Acknowledgments

The authors; K M Dawood and A A Abbas are greatly indebted to Faculty of Science, Cairo University, for the facilities offered to them. M. H. Abdellattif is indebted to Taif University Researches Supporting Project Number (TURSP-2020/91), Taif University, Taif, Saudi Arabia.

Article highlights

• Various bipyrazole heterocyclic systems were reported as highly potent anticancer, anti-inflammatory, antimicrobial, antitubercular, and selective enzymes inhibitors.

• A large number of pyrazole derivatives are broadly common in several commercial drugs in the market.

• Most of the biologically active bipyrazole derivatives had higher potencies than the corresponding reference drugs against a number of diseases with high safety margin and pharmacokinetic suitability for oral use.

• Some bipyrazoles exhibited much better anti-inflammatory activity with very low ulcerogenic effect compared to Indomethacin drug and can be considered as interesting candidates for drug trials.

• Chloroquine is an antimalarial and possible COVID-19 drug. Some bipyrazoles had better antimalarial activity than Chloroquine, thus bipyrazoles might be possible COVID-19 inhibitors.

• The pharmacological activities of bipyrazoles were greatly affected by the type of the substituents at N- and C- positions as disclosed by Structure activity relationship (SAR) studies.

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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 was not funded.