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Conformational Restriction: An Effective Tactic in ‘Follow-On’-Based Drug Discovery

2014; Future Science Ltd; Volume: 6; Issue: 8 Linguagem: Inglês

10.4155/fmc.14.50

1756-8927

Zengjun Fang, Yuning Song, Peng Zhan, Qingzhu Zhang, Xinyong Liu,

Chemical Synthesis and Analysis

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.