Abstract
The conformational restriction (rigidification) of a flexible ligand has often been a commonly used strategy in drug design, as it can minimize the entropic loss associated with the ligand adopting a preferred conformation for binding, which leads to enhanced potency for a given physiological target, improved selectivity for isoforms and reduced the possibility of drug metabolism. Therefore, the application of conformational restriction strategy is a core aspect of drug discovery and development that is widely practiced by medicinal chemists either deliberately or subliminally. The present review will highlight current representative examples and a brief overview on the rational design of conformationally restricted agents as well as discuss its advantages over the flexible counterparts.
Financial & competing interests disclosure
The authors wish to acknowledge financial support from the National Natural Science Foundation of China (NSFC No.81102320, No.81273354), Research Fund for the Doctoral Program of Higher Education of China (No. 20110131130005, 20110131120037), and China Postdoctoral Science Foundation funded project (No.20100481282, No.2012T50584). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.