Two- and Three-dimensional Rings in Drugs
Article first published online: 18 MAR 2014
© 2013 The Authors Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Chemical Biology & Drug Design
Volume 83, Issue 4, pages 450–461, April 2014
How to Cite
Aldeghi, M., Malhotra, S., Selwood, D. L. and Chan, A. W. E. (2014), Two- and Three-dimensional Rings in Drugs. Chemical Biology & Drug Design, 83: 450–461. doi: 10.1111/cbdd.12260
- Issue published online: 18 MAR 2014
- Article first published online: 18 MAR 2014
- Accepted manuscript online: 7 NOV 2013 02:08AM EST
- Manuscript Accepted: 4 NOV 2013
- Manuscript Revised: 24 SEP 2013
- Manuscript Received: 31 MAY 2013
- lead optimization;
Using small, flat aromatic rings as components of fragments or molecules is a common practice in fragment-based drug discovery and lead optimization. With an increasing focus on the exploration of novel biological and chemical space, and their improved synthetic accessibility, 3D fragments are attracting increasing interest. This study presents a detailed analysis of 3D and 2D ring fragments in marketed drugs. Several measures of properties were used, such as the type of ring assemblies and molecular shapes. The study also took into account the relationship between protein classes targeted by each ring fragment, providing target-specific information. The analysis shows the high structural and shape diversity of 3D ring systems and their importance in bioactive compounds. Major differences in 2D and 3D fragments are apparent in ligands that bind to the major drug targets such as GPCRs, ion channels, and enzymes.