2026, Vol. 7, Issue 2, Part A

Amide functionalities play a pivotal role in modern drug discovery due to their chemical robustness, biological compatibility, and widespread presence in approved pharmaceuticals. Among them, carboxamide and acetamide derivatives represent two closely related yet distinct functional motifs that are frequently employed to modulate biological activity, pharmacokinetics, and clinical performance of small-molecule drugs. Despite their extensive and long-standing use, comparative discussions focusing specifically on their biological and pharmacological relevance remain limited. This review provides a consolidated comparison of carboxamide and acetamide derivatives from a biological perspective, emphasizing reported biological activities, pharmacokinetic and ADMET behaviour, safety profiles, and clinical relevance across therapeutic areas. By integrating data from approved drugs, clinical candidates, and preclinical studies, this review aims to support informed functional-group selection during drug design and optimization, highlighting the complementary roles of carboxamide and acetamide motifs in contemporary pharmaceutical research.