Phenol (bio)isosteres in drug design and development.

Autor: Dunker C; European Institute for Molecular Imaging (EIMI), University of Muenster, Muenster, Germany.; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany., Schlegel K; European Institute for Molecular Imaging (EIMI), University of Muenster, Muenster, Germany., Junker A; European Institute for Molecular Imaging (EIMI), University of Muenster, Muenster, Germany.; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2024 Nov 24, pp. e2400700. Date of Electronic Publication: 2024 Nov 24.
DOI: 10.1002/ardp.202400700
Abstrakt: Due to their versatile properties, phenolic compounds are integral to various biologically active molecules, including many pharmaceuticals. However, their application in drug design is often hindered by issues such as poor oral bioavailability, rapid metabolism, and potential toxicity. This review explores the use of phenol bioisosteres-structurally similar compounds that can mimic the biological activity of phenols while potentially offering improved drug-like properties. We provide an extensive analysis of various phenol bioisosteres, including benzimidazolones, benzoxazolones, indoles, quinolinones, and pyridones, highlighting their impact on the pharmacokinetic and pharmacodynamic profiles of drugs. Case studies illustrate the successful application of these bioisosteres in enhancing metabolic stability, receptor selectivity, and overall therapeutic efficacy. Additionally, the review addresses the challenges associated with phenol bioisosterism, such as maintaining potency and avoiding undesirable side effects. By offering a detailed examination of current strategies and potential future directions, this review serves as a valuable resource for medicinal chemists seeking to optimize phenolic scaffolds in drug development. The insights provided herein aim to facilitate the design of more effective and safer therapeutic agents through strategic bioisosteric modifications.
(© 2024 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
Externí odkaz: