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

Fang, Zengjun, Song, Yu’ning, Zhan, Peng, Zhang, Qingzhu, Liu, Xinyong·2014·Future Medicinal Chemistry

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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.

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Authors: Fang, Z., Song, Y., Zhan, P., Zhang, Q., & Liu, X.
Venue: Future Medicinal Chemistry
Publisher: Informa UK Limited
Published: 2014-05
Volume: 6
Issue: 8
Pages: 885-901
ISSN: 1756-8919 (ISSN-L)
1756-8927
DOI: 10.4155/fmc.14.50
OpenAlex: W2071358460
Cited by: 268
References: 58
FWCI: 2.92
Type: journal article
Language: en
Open access: closed

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

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