Exploring USFDA‐Approved Imidazole‐Based Small Molecules in Drug Discovery: A Mini Perspective
Sonali Gupta, Marianesan Arockia Babu, Roshan Kumar, Thakur Gurjeet Singh, Anjali Goel, Sameer Rastogi, Pankaj Kumar Sharma, Yogita Tyagi, Kapil Kumar Goel, Bhupinder Kumar · Chemistry & Biodiversity · 2025
In the present work, we have explored the importance of the imidazole ring and its importance in drug discovery, citing the key approvals in the present decade (2013-2024). The pharmacological attribution for the approved drugs revealed that out of 20 approved drugs, 45% of the approvals were made as anti-infectives, followed by approvals under the category of genetic and metabolic disorders, sexual endocrine disorders, anticancer, and to treat blood pressure, gastrointestinal disorders, and neurological conditions. Most approved drugs were dispensed through solid dosage forms (13) and thus had predominantly oral routes beside others. The metabolism pattern revealed that the drugs undergo metabolism via the involvement of multiple enzymes, where CYP3A4 and CYP3A5 were the core enzymes. The excretion pattern of these drugs revealed that the drugs are majorly excreted via the fecal route. The chemical analysis showed that pyrrolidine/pyrrole was the major heterocycle in the approved drugs, followed by the indole ring in the hybridization. Considering the substitution pattern, most drugs possessed amide, amines, and fluoro group as the functional substitution with the 2,4-substitution pattern seen in most approved drugs. Besides this, the three approved drugs were found to possess chiral centers and exhibit chirality. The article also expanded to cover the synthetic routes and metabolic routes for this versatile ring system and case studies for its utility to serve as bioisostere in drug discovery. Furthermore, this article also presents the receptor-ligand interactions of imidazole-based drugs with various target receptors. The present article is, therefore, put forth to assist medicinal chemists and chemists working in drug discovery of this versatile ring system.