Heterocyclic Compounds as Dipeptidyl Peptidase-IV Inhibitors with Special Emphasis on Oxadiazoles as Potent Anti-Diabetic Agents

Abstract

Dipeptidyl peptidase-IV (DPP-IV) inhibitors, often known as gliptins, have been used to treat type 2 diabetes mellitus (T2DM). They may be combined with other medications as an additional treatment or used alone as a monotherapy. In addition to insulin, sulfonylureas, thiazolidinediones, and metformin, these molecules appear as possible therapeutic options. Oxadiazole rings have been employed in numerous different ways during drug development efforts. It has been shown that including them in the pharmacophore increases the amount of ligand that may be bound. The exceptional hydrogen bond acceptor properties of oxadiazoles and the distinct hydrocarbon bonding potential of their regioisomers have been established. Beside their anti-diabetic effects, oxadiazoles display a wide range of pharmacological properties. In this study, we made the assumption that molecules containing oxadiazole rings may afford a different approach to the treatment of diabetes, not only for controlling glycemic levels but also for preventing atherosclerosis progression and other complications associated with diabetes. It was observed that oxadiazole fusion with benzothiazole, 5-(2,5,2-trifluoroethoxy) phenyl, β-homophenylalanine, 2-methyl-2-{5-(4-chlorophenyl), diamine-bridged bis-coumarinyl, 5-aryl-2-(6′-nitrobenzofuran-2′-yl), nitrobenzofuran, and/or oxindole leads to potential anti-diabetic activity.

Room Temperature Synthesis of Bioactive 1,2,4-Oxadiazoles

“…[ 7 , 8 , 9 , 10 , 11 , 12 ]). The interesting feature of the 1,2,4-oxadiazole moiety from a medicinal chemistry viewpoint is its potential coverage of a broad spectrum of therapeutic areas, including oncology [ 13 , 14 , 15 ], immunology [ 16 ], neurology [ 17 , 18 , 19 , 20 ], infectious diseases [ 21 , 22 , 23 , 24 ], metabolism and endocrinology [ 25 , 26 , 27 , 28 ], urology [ 29 , 30 ], gastroenterology [ 31 ], cardiology [ 32 ], rheumatology [ 33 ], and respirology [ 34 ]. Such versatility of the 1,2,4-oxadiazole motif, in our opinion, is due to its recognition as the hydrolytically stable bioisostere of the amide and ester bonds [ 35 , 36 , 37 , 38 , 39 ].…”

Coumarin-Based Sulfonamide Derivatives as Potential DPP-IV Inhibitors: Pre-ADME Analysis, Toxicity Profile, Computational Analysis, and In Vitro Enzyme Assay

“…Several new anti-diabetic medications, such as 11b-hydroxysteroid dehydrogenase 1 blockers, sodium-glucose co-transporter 2 blockers, insulin analogues, glucagon antagonists, and dipeptidyl peptidase-IV (DPP-IV) inhibitors, have been discovered to address these undesirable effects [ 7 ]. Glucokinase activators and insulin-releasing enhancers are two examples of these novel therapies [ 8 , 9 ].…”

Thiol-promoted intermolecular cyclization to synthesize 1,2,4-oxadiazoles including tioxazafen under transition metal-free conditions

“…1 Among various heterocyclic compounds, substituted 1,2,4-oxadiazoles have been widely researched due to their worthy applications ranging from pharmacophore 2 to functional materials. 3 Furthermore, the widespread use of 1,2,4-oxadiazole as a scaffold in medicinal chemistry establishes this skeleton as a component of the privileged structure, and its derivatives show a wide range of biological activities, 4 such as anticancer, 5 anti-inflammatory, 6 anti-diabetic, 7 anti-parasitic, 8 and antibacterial 9 (Fig. 1).…”