On the origins of three-dimensionality in drug-like molecules.
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Date
2016-09Author
Meyers, J
Carter, M
Mok, NY
Brown, N
Type
Journal Article
Metadata
Show full item recordAbstract
Aim Many medicinal chemistry-relevant structures and core scaffolds tend toward geometric planarity, which hampers the optimization of physicochemical properties desirable in drug-like molecules. As challenging drug target classes emerge, the exploitation of molecular three-dimensionality in lead optimization is becoming increasingly important. While recent interest has emphasized the importance of enhanced three-dimensionality in molecular fragment designs, the extent to which this is required in core scaffolds remains unclear.Materials & methods Three computational methods, Scaffold Tree deconstruction, Synthetic Disconnection Rules retrosynthetic deconstruction and virtual library enumeration, are applied, together with the descriptors plane of best fit and principal moments of inertia, to investigate the origins of three-dimensionality in drug-like molecules.Conclusion This study informs on the stage at which molecular three-dimensionality should be considered in drug design.
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Subject
Humans
Pharmaceutical Preparations
Molecular Structure
Drug Design
Chemistry, Pharmaceutical
Small Molecule Libraries
Research team
Medicinal Chemistry 1
Language
eng
License start date
2016-09
Citation
Future medicinal chemistry, 2016, 8 (14), pp. 1753 - 1767