Chinese Journal of Organic Chemistry >
Research Progress of Covalent Inhibitors
Received date: 2018-04-10
Revised date: 2018-06-19
Online published: 2018-07-24
Supported by
Project supported by the National Key Research and Development Program of China (No. 2017YFA0505200), the National Key Fundamental Research and Development of China (973 Program, No. 2015CB856200), the National Natural Science Foundation of China (Nos. 21472010, 21521003, 21561142002, 21625201).
The development of covalent inhibitors plays a major role in recent drug discovery due to their potential excellent pharmacokinetics. Covalent inhibitors are small organic molecules which interact with specific target proteins and form a covalent bond, resulting an alteration of the protein conformation and subsequently inhibit the protein activity. The modifications of proteins by covalent inhibitors are generally irreversible with some exceptions. In this review, the commercial covalent inhibitors that interact with proteins via Michael additions, nucleophilic substitution, or disulfide linkage are reviewed. The discussion on various types of warheads in covalent inhibitors could inspire future rational drug design.
Key words： covalent inhibitors; warheads; drug design
Dong Haoran, Subiding Tayier, Wang Xin, Lei Xiaoguang . Research Progress of Covalent Inhibitors[J]. Chinese Journal of Organic Chemistry, 2018 , 38(9) : 2296 -2306 . DOI: 10.6023/cjoc201804018
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