Medicinal Chemistry Perspectives on Multi‐Targeted Antidiabetic Agents: A Comprehensive Review

ABSTRACT

Diabetes mellitus is a multifactorial metabolic disease, characterized by chronic hyperglycemia; it produces significant long‐term complications affecting several organs. Despite the availability of number of antidiabetic agents with single target therapy often suffers from limitations like resistance, side effects, reduced efficacy, and adverse effects. In recent years, multi targeted therapies are attracting attention due to their ability to modify multiple target effects simultaneously, enhance glycemic control with minimum side effects and complications. This review compiles dual targeted or multiple targeted scaffolds that are targeting Peroxisome Proliferator‐Activated Receptor (PPAR) subtypes, Dipeptidyl Peptidase‐IV (DPP IV) in combination with incretin‐based receptors like Glucagon‐Like Peptide‐1 (GLP‐1), G protein‐coupled receptor 119 (GPR119), G‐protein‐coupled receptor 40 (GPR40), Aldose reductase enzyme and oxidative enzyme. Authors have analyzed research carried out over the past decade on dual scaffold such as flavonoids, coumarins, oxindoles, indoles, benzothiazoles, anthranilic acid, and other heterocyclic derivatives. Authors have also discussed the medicinal chemistry of these heterocyclic derivatives with their SAR. A dual‐acting and multiple target strategy provides a viable approach for development of safer and more effective therapies.