Boron‐Based Bioisosteres in Medicinal Chemistry: Advances in Heterocycles and Therapeutic

Abstract

Boron‐containing compounds have become an important class of scaffolds in medicinal chemistry, broadening the chemical space available for drug discovery. This review summarizes progress and key advances reported over the past 5 years in the development of bioactive boron‐based heterocycles and related systems, including BN‐indoles, azaborines, benzoxazaborines, benzodiazaborines, benzoxaborinines, benzoxaboroles, and boronic acid derivatives. These motifs act as bioisosteres of carbon frameworks and impart distinct physicochemical properties such as increased polarity, improved solubility, and enhanced hydrogen‐bonding capabilities. Several examples highlight their therapeutic relevance. Azaborine‐based histone deacetylase (HDAC) inhibitors and BN‐indole derivatives show potent nanomolar enzyme inhibition. Benzoxaboroles have reached clinical relevance, including antifungal drugs such as tavaborole and crisaborole, as well as late‐stage candidates like epetraborole and acoziborole. Benzoxaborinines and olaparib isosteres exhibit activity against carbonic anhydrases and PARP enzymes, while boronic acid drugs such as bortezomib and ixazomib are established proteasome inhibitors used in cancer therapy. Additional applications include antiviral, antibacterial, antiparasitic, and anti‐inflammatory activities, for example Leishmania CPSF3 inhibitors and P2X7 receptor antagonists. Despite these advances, challenges remain regarding potency, pharmacokinetics, and mechanistic understanding of boron–target interactions. Overall, boron‐based bioisosteres represent a versatile platform for developing new therapeutics across diverse disease areas.