A ring-bracing approach to computer-assisted ligand design

✍ Scribed by Andrew R. Leach; Richard A. Lewis

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 672 KB
• Volume: 15
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/jcc.540150213

✦ Synopsis

Rigid inhibitors suffer a smaller loss of conformational entropy when they bind to a macromolecular receptor than fheir acyclic counterparts. They can also be useful for elucidating pharmacophores due to their reduced conformational space and may be more amenable to synthesis. Computational approaches to rational drug design should therefore take these factors into consideration when suggesting possible compounds. We describe how an acyclic chain which links two parts of a receptor site can be 'braced' using ring templates. The acyclic chains may be produced from a number of sources, including lattices or the structures of known inhibitors. The resulting structures contain a rich variety of isolated and fused ring systems, which provide many useful molecular skeletons for subsequent inhibitor design.