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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Kumari S,Carmona AV,Tiwari AK,Trippier PCdoi
10.1021/acs.jmedchem.0c00530subject
Has Abstractpub_date
2020-11-12 00:00:00pages
12290-12358issue
21eissn
0022-2623issn
1520-4804journal_volume
63pub_type
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