BACKGROUND The carboxylic acid moiety is an important functional group which features in the pharmacophore of some 450 drugs. Unfortunately, some carboxylic acid-containing drugs have been withdrawn from market due to unforeseen toxicity issues. Other issues associated with the carboxylate moiety include reduced metabolic stability or limited passive diffusion across biological membranes. Medicinal chemists often turn to bioisosteres to circumvent such obstacles. OBJECTIVE The aim of this review is to provide a summary of the various applications of novel carboxylic acid bioisosteres which have appeared in the literature since 2013. RESULTS We have summarised the most recent developments in carboxylic acid bioisosterism. In particular, we focus on the changes in bioactivity, selectivity or physicochemical properties brought about by these substitutions, as well as the advantages and disadvantages of each isostere. CONCLUSION The topics discussed herein highlight the continued interest in carboxylate bioisosteres. The development of novel carboxylic acid substitutes which display improved pharmacological profiles is a testament to the innovation and creativity required to overcome the challenges faced in modern drug design.

中文翻译：

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新型羧酸生物等排体实际应用的最新进展。

背景羧酸部分是一种重要的官能团，在大约450种药物的药效团中具有特征。不幸的是，由于不可预见的毒性问题，一些含羧酸的药物已经退出市场。与羧酸盐部分相关的其他问题包括代谢稳定性降低或跨生物膜的被动扩散受限。药物化学家经常求助于生物等排体来规避这些障碍。目的 本综述的目的是总结 2013 年以来在文献中出现的新型羧酸生物等排体的各种应用。结果 我们总结了羧酸生物等排体的最新发展。特别是，我们关注生物活性的变化，这些取代带来的选择性或物理化学性质，以及各等排体的优缺点。结论 本文讨论的主题突出了对羧酸盐生物等排体的持续兴趣。开发显示出改进的药理特性的新型羧酸替代品证明了克服现代药物设计面临的挑战所需的创新和创造力。