2‐Isoxazolines: A Synthetic and Medicinal Overview. (19th November 2020)

• Record Type: Journal Article
• Authors: Kumar, Gulshan; Shankar, Ravi
• Is Part Of: ChemMedChem. Volume 16:Number 3(2021)
• Page Start: 430
• Page End: 447
• Publication Date: 2020-11-19
• Subjects: Isoxazolines -- natural products -- synthetic analogues -- 1, 3-dipolar cycloaddition -- biological activity -- clinical trials; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202000575
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Isoxazolines are nitrogen‐ and oxygen‐containing five‐membered heterocyclic scaffolds with extensive biological activities. This framework can be readily obtained in good to excellent yields through 1, 3‐dipolar cycloaddition between nitrones with alkynes or allenes, aryl/alkyl halides, alkynes, and oxaziridines under mild conditions. This scaffold has been an emerging area of interest for many researchers given their wide range of bioactivities. Herein we review synthetic strategies toward isoxazolines and the role these efforts have had in enhancing the biological activity of natural products and synthetic compounds such as antitubercular agents, COX‐1 inhibitors, COX‐2 inhibitors (e. g., valdecoxib), nicotinic receptor modulators, and MIF inhibitors. With a focus on efforts from 2010 onward, this review provides in‐depth coverage of the design and biological evaluation of isoxazoline systems and their impact on various pathologies. Abstract : Tremendous work has been done in recent years toward the synthesis of isoxazoline‐based derivatives, as they are an active pharmacophore class in the field of medicinal chemistry. When derivatized with the isoxazoline motif as a core unit, both natural and synthetic molecules are found to exhibit a wide range of biological activities. The isoxazoline moiety is present in various drugs currently in clinical use, such as lotilaner, fluralaner, sarolaner, and afoxolaner. This review covers a wide scope of the literature related to various metal‐free and metal‐catalyzed syntheses of isoxazolines, along with studies into the biological profiles of isoxazoline‐based compounds.