紧凑而多功能的氧杂环丙烷基团在药物发现和药物化学研究中引起了极大的关注。本综述文章概述了氧杂环丙烷在临床和临床前候选药物中的广泛应用，针对癌症、病毒感染、自身免疫性疾病、神经退行性疾病、代谢性疾病等各种人类疾病进行了目标定位。重点讨论了生物活性氧杂环丙烷基化合物及其与疾病相关的靶点，如激酶、表观遗传和非表观遗传酶以及受体。本综述还详细描述了氧杂环丙烷基团对一些重要性能的影响，包括溶解度、亲脂性、pKa值、P-糖蛋白（P-gp）外排、代谢稳定性、构象偏好、毒性特性（例如细胞色素P450（CYP）抑制和人类-麻痹-去相关基因（hERG）抑制）以及药物动力学（PK）性质、药效、靶向选择性。我们预计，本研究将提供有价值的见解，推动新型生物活性氧杂环丙烷基小分子的未来发现，使其能够有效应用于各种人类疾病的治疗。版权所有©2023 Elsevier Masson SAS。保留所有权利。

The compact and versatile oxetane motifs have gained significant attention in drug discovery and medicinal chemistry campaigns. This review presents an overview of the diverse applications of oxetanes in clinical and preclinical drug candidates targeting various human diseases, including cancer, viral infections, autoimmune disorders, neurodegenerative conditions, metabolic disorders, and others. Special attention is given to biologically active oxetane-containing compounds and their disease-related targets, such as kinases, epigenetic and non-epigenetic enzymes, and receptors. The review also details the effect of the oxetane motif on important properties, including aqueous solubility, lipophilicity, pKa, P-glycoprotein (P-gp) efflux, metabolic stability, conformational preferences, toxicity profiles (e.g., cytochrome P450 (CYP) suppression and human ether-a-go-go related gene (hERG) inhibition), pharmacokinetic (PK) properties, potency, and target selectivity. We anticipate that this work will provide valuable insights that can drive future discoveries of novel bioactive oxetane-containing small molecules, enabling their effective application in combating a wide range of human diseases.Copyright © 2023 Elsevier Masson SAS. All rights reserved.