The 1,2,3-triazole ‘all-in-one’ ring system in drug discovery: a good bioisostere, a good pharmacophore, a good linker, and a versatile synthetic tool

ABSTRACT

Introduction

The 1,2,3-triazole ring occupies an important space in medicinal chemistry due to its unique structural properties, synthetic versatility and pharmacological potential making it a critical scaffold. Since it is readily available through click chemistry for creating compound collections against various diseases, it has become an emerging area of interest for medicinal chemists.

Areas covered

This review article addresses the unique properties of the1,2,3-triazole nucleus as an intriguing ring system in drug discovery while focusing on the most recent medicinal chemistry strategies exploited for the design and development of 1,2,3-triazole analogs as inhibitors of various biological targets.

Expert opinion

Evidently, the 1,2,3-triazole ring with unique structural features has enormous potential in drug design against various diseases as a pharmacophore, a bioisoster or a structural platform. The most recent evidence indicates that it may be more emerging in drug molecules in near future along with an increasing understanding of its prominent roles in drug structures. The synthetic feasibility and versatility of triazole chemistry make it certainly ideal for creating compound libraries for more constructive structure-activity relationship studies. However, more comparative and target-specific studies are needed to gain a deeper understanding of the roles of the 1,2,3-triazole ring in molecular recognition.

KEYWORDS:

• 1
• 2
• 3-triazole
• bioisostere
• pharmacophore
• linker
• synthetic tool

Article highlights

• The appearance of the 1,2,3-triazole heterocyclic scaffold in the structures of experimental compounds with various pharmacological activities as well as in several clinical drug molecules has gained a momentum recently.

• The 1,2,3-triazole ring is primarily exploited as a bioisostere and a linker but its role as a pharmacophore has only recently emerged.

• Several studies suggest that the triazole ring should be approached with caution in terms of its use as an amide bioisostere.

• Although metabolic stability prospects or CYP inhibitor properties of the 1,2,3-triazole derivatives are briefly investigated, it requires more experimental evidence to be evaluated in structure optimization studies.

• Recent advances reveal promising prospects of 1,2,3-triazoles that contribute to the anticancer, antimicrobial, antiviral and anti-inflammatory drug discovery, as well as their use for target-specific enzyme inhibitors or receptor antagonists.

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 dislosure

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

Additional information

Funding

This paper was not funded.