The DOI matches its Crossref record; 194 of the 194 references it cites were found in a registry or an index.
Bioisosteres of the Phenyl Ring: Recent Strategic Applications in Lead Optimization and Drug Design
Open accessAbstract
The benzene moiety is the most prevalent ring system in marketed drugs, underscoring its historic popularity in drug design either as a pharmacophore or as a scaffold that projects pharmacophoric elements. However, introspective analyses of medicinal chemistry practices at the beginning of the 21st century highlighted the indiscriminate deployment of phenyl rings as an important contributor to the poor physicochemical properties of advanced molecules, which limited their prospects of being developed into effective drugs. This Perspective deliberates on the design and applications of bioisosteric replacements for a phenyl ring that have provided practical solutions to a range of developability problems frequently encountered in lead optimization campaigns. While the effect of phenyl ring replacements on compound properties is contextual in nature, bioisosteric substitution can lead to enhanced potency, solubility, and metabolic stability while reducing lipophilicity, plasma protein binding, phospholipidosis potential, and inhibition of cytochrome P450 enzymes and the hERG channel.
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Cites
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Self-citationFluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design
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Self-citationRings in Drugs: Miniperspective
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Metadata
- Authors
- Subbaiah, M. A. M., & Meanwell, N. A.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-09-30
- Volume
- 64
- Issue
- 19
- Pages
- 14046-14128
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W3203279400
- Cited by
- 710
- References
- 194
- FWCI
- 42.24
- Type
- journal article
- Language
- en
- Open access
- green
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