Title:Recent Developments in the Practical Application of Novel Carboxylic
Acid Bioisosteres
Volume: 29
Issue: 13
Author(s): Conor Horgan and Timothy P. O’Sullivan*
Affiliation:
- School of Chemistry, University College Cork, Cork, Ireland
- Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland
- School of Pharmacy, University College Cork,
Cork, Ireland
Keywords:
Isosteres, bioisosterism, carboxylic acids, drug design, acidity, lipophilicity.
Abstract:
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acid-containing drugs have been withdrawn from market due to unforeseen toxicity issues.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.