Amide Bond Bioisosteres: Strategies, Synthesis, and Successes

Shikha Kumari, Angelica V. Carmona, Amit K. Tiwari, Paul C. Trippier

Research output: Contribution to journalReview articlepeer-review

274 Scopus citations


The amide functional group plays a key role in the composition of biomolecules, including many clinically approved drugs. Bioisosterism is widely employed in the rational modification of lead compounds, being used to increase potency, enhance selectivity, improve pharmacokinetic properties, eliminate toxicity, and acquire novel chemical space to secure intellectual property. The introduction of a bioisostere leads to structural changes in molecular size, shape, electronic distribution, polarity, pKa, dipole or polarizability, which can be either favorable or detrimental to biological activity. This approach has opened up new avenues in drug design and development resulting in more efficient drug candidates introduced onto the market as well as in the clinical pipeline. Herein, we review the strategic decisions in selecting an amide bioisostere (the why), synthetic routes to each (the how), and success stories of each bioisostere (the implementation) to provide a comprehensive overview of this important toolbox for medicinal chemists.

Original languageEnglish (US)
Pages (from-to)12290-12358
Number of pages69
JournalJournal of Medicinal Chemistry
Issue number21
StatePublished - Nov 12 2020

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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