Amide Bond Bioisosteres: Strategies, Synthesis, and Successes.

Journal of Medicinal Chemistry
Shikha KumariPaul C Trippier

Abstract

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.

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Citations

Jan 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Roberto SoleValentina Beghetto
Mar 17, 2021·European Journal of Medicinal Chemistry·Zezhong LiHuchen Zhou
Mar 30, 2021·Bioorganic & Medicinal Chemistry Letters·Ming-Jie HuangHong-Min Liu
Apr 7, 2021·European Journal of Medicinal Chemistry·Karol R FranciscoCarlo Ballatore
Apr 17, 2021·ACS Medicinal Chemistry Letters·Nathalie M GrobThomas L Mindt
May 1, 2021·Journal of the American Chemical Society·Wataru Muramatsu, Hisashi Yamamoto
May 14, 2021·Frontiers in Chemistry·Paweł J Czerwiński, Bartłomiej Furman
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Serena MontanariAngela Rampa
Jun 25, 2021·Chemical Reviews·Anand K AgrahariVinod K Tiwari
Jul 20, 2021·Journal of Agricultural and Food Chemistry·Dongguo XiaXianhai Lv
Jul 27, 2021·Organic & Biomolecular Chemistry·Huifang LaiDaijun Zha
Aug 27, 2021·Journal of Medicinal Chemistry·Md Shafikur RahmanPaul C Trippier
Sep 3, 2021·Journal of Medicinal Chemistry·Antonino N FallicaValeria Pittalà
Sep 5, 2021·The Journal of Organic Chemistry·Guillaume Reynard, Hélène Lebel
Sep 28, 2021·ACS Omega·Rajendra R KshirsagarVijayaparthasarathi Vijayakumar
Aug 31, 2021·Chemistry : a European Journal·Ferdinand H Lutter, Matthieu Jouffroy
Oct 8, 2021·Chemistry : a European Journal·Xiao-Feng WuHui-Qing Geng
Nov 2, 2021·Journal of Medicinal Chemistry·Mariateresa GiustinianoPaul C Trippier
Nov 11, 2021·Organic & Biomolecular Chemistry·Volkan FındıkSafiye Sag Erdem

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