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2000
Volume 25, Issue 12
  • ISSN: 1389-5575
  • E-ISSN: 1875-5607

Abstract

This mini-review summarizes the structure-property relationships of seven small-molecule drugs approved in 2024, providing insights into effective lead-to-candidate optimization strategies. The analysis focused on aprocitentan, flurpiridaz F-18, inavolisib, vorasidenib, ensitrelvir, golidocitinib, and zorifertinib, highlighting the key structural modifications that enhanced their drug-like properties. Notable optimization strategies included the strategic use of five- and six-membered nitrogen-containing heterocycles as cyclic bioisosteres and solubilizing groups. For the kinase inhibitor golidocitinib, the unique position of a solubilizing group within the binding pocket achieved dual benefits, , enhanced target selectivity and physicochemical properties. When developing central nervous system-penetrant drugs such as zorifertinib, careful control of rotatable bonds, hydrogen bond donors, and molecular lipophilicity was critical for optimizing blood-brain barrier penetration while remaining suitable for oral administration. These findings on structure-property relationships offer valuable guidance for future drug development, particularly in addressing challenges related to solubility, bioavailability, and tissue-specific drug distribution.

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2025-11-01

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Structure-Property Relationships Reported for the New Drugs Approved in 2024
Mini Rev Med Chem 25, 911 (2025); https://doi.org/10.2174/0113895575390155250711072709
/content/journals/mrmc/10.2174/0113895575390155250711072709
/content/journals/mrmc/10.2174/0113895575390155250711072709
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  • Article Type:     Review Article
Keyword(s): bioisosteres; candidate selection; drug discovery; heterocycles; lead optimization; Structure-property relationship

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