ABSTRACT Halogens are utilized in drug discovery and development due to their ability to precisely tune the molecular properties of drug candidates. The halogen substituents play a crucial role in determining the stability, lipophilicity, and receptor binding, as well as significantly influencing the metabolic fate of the drug candidates. Literature insights reveal that 30% of all small molecules approved by the USFDA carry a halogen as a substituent. Considering the vital importance of halogen‐containing substituents, we have compiled concise information on halogen‐containing US FDA‐approved drugs over the last decade (2019–2024). The articles provide information on pharmacological conditions, targets, available formulations, and pharmacokinetic details for each approved drug that possesses a halogen as a substituent, along with its corresponding chemical structure. The analysis revealed that 37 new drugs were approved to combat cancer (13), followed by rare diseases (6), viral infections (3), and other conditions during the analysis period. Furthermore, the chemistry of halogens, along with their medicinal applications, provides key evidence on how halogens have been explored to enhance the pharmacokinetics and pharmacodynamics of drug candidates. The analysis of approved dosage forms revealed that 23 were solid dosage forms, comprising 24 tablet forms, 8 capsules, and 1 powder. CYP3A4 is a major contributor in the metabolism of 6 drugs, followed by CYP3A (3), CYP1A2 (2), CYP3A4/5 (2), and one each by CYP2C9, UGT1A9, CYP2C8, aldehyde oxidase, and other non‐CYP enzymes. The present medicinal chemistry perspective is thus expected to be a valuable read for the medicinal and allied sciences community.
Ali et al. (Thu,) studied this question.