The vinyl sulfone motif as a structural unit for novel drug design and discovery

ABSTRACT

Introduction

Vinyl sulfones are a special sulfur-containing structural unit that have attracted considerable attention, owing to their important role in serving as key structural motifs of various biologically active compounds as well as serving as versatile building blocks for organic transformations. The synthetic strategy of vinyl sulfone derivatives has been substantially upgraded over the past 30 years, and the wide application of this functional group in drug design and discovery has been promoted.

Area Covered

In this review, the authors review the application of vinyl sulfones in drug discovery and select optimized compounds which might have significant impact or potential inspiration for drug design.

Expert opinion

Vinyl sulfones have been reported to target various macromolecular targets via non-covalent or covalent interactions, including multiple kinases, tubulin, cysteine protease, transcription factor, and so on. Thus, it has been significantly applied as a privileged scaffold in the design of anticancer, anti-infective, anti-inflammatory, and neuroprotective agents. However, much work remains to be done to improve the drug-like properties, such as chemical and metabolic stability, ADME, and toxicity. Besides, the chemical space of vinyl sulfones needs to be expanded, including but not limited to the design of constrained endocyclic and exocyclic vinyl sulfones.

KEYWORDS:

• Vinyl sulfone
• Targeted covalent inhibitor
• Drug design
• Kinase inhibitor
• Chemical probe

Article highlights

• Vinylsulfones have widely existed in a variety of biologically active compounds and building blocks in synthetic organic chemistry

• As a bioisostere ofenone, vinyl sulfones can be applicable for achieving various biological activities from chalcones

• Vinyl sulfones could target diverse proteins via non-covalent or covalent interactions, including multiple kinases, tubulin, cysteine protease, transcription factor, etc.

• Vinyl sulfones show great potential in the treatment of cancer, infective, inflammatory, and neurodegenerative diseases.

• Due to the unique properties to form covalent bonds with cysteine, lysine, and serine residues, it might find wide application in targeted covalent inhibitor design.

Declaration of interest

The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

The authors are funded by the Sichuan Science and Technology Program (Grant No. 2022NSFSC0619).