Conor Horgan and Timothy P. O’ Sullivan*
Background: The carboxylic acid 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 Unfortunately, some carboxylic acid-containing drugs have been withdrawn from market due to unforeseen toxicity issues.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 physiochemical 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 testament to the innovation and creativity required to overcome the challenges faced in modern drug design.
Isosteres, bioisosterism, carboxylic acids, drug design, acidity, lipophilicity
School of Chemistry, University College Cork, Cork, School of Chemistry, University College Cork, Cork