title: Conformational restriction: an effective tactic in 'follow-on'-based drug discovery.
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.
authors: Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, P. R. China.
authors: Zengjun
authors: Z
authors: Fang
authors: Yu'ning
authors: Y
authors: Song
authors: Peng
authors: P
authors: Zhan
authors: Qingzhu
authors: Q
authors: Zhang
authors: Xinyong
authors: X
authors: Liu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019380:Anti-HIV Agents / Q000737:chemistry / Q000627:therapeutic use; D015195:Drug Design; D055808:Drug Discovery; D015658:HIV Infections / Q000188:drug therapy; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use; D054387:Receptors, CXCR / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D018696:Neuroprotective Agents; D054387:Receptors, CXCR; D053829:Amyloid Precursor Protein Secretases; D016333:HIV Protease