On the origins of three-dimensionality in drug-like molecules.
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ICR Authors
Authors
Meyers, J
Carter, M
Mok, NY
Brown, N
Carter, M
Mok, NY
Brown, N
Document Type
Journal Article
Date
2016-09
Date Accepted
Abstract
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.
Citation
Future medicinal chemistry, 2016, 8 (14), pp. 1753 - 1767
Rights
Source Title
Publisher
ISSN
1756-8919
eISSN
1756-8927
Collections
Research Team
Medicinal Chemistry 1