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Profound Methyl Effects in Drug Discovery and a Call for New CH Methylation Reactions
Author(s) -
Schönherr Heike,
Cernak Tim
Publication year - 2013
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201303207
Subject(s) - methylation , drug discovery , chemistry , methyl group , magic (telescope) , stereochemistry , small molecule , drug , molecule , computational biology , alkyl , combinatorial chemistry , medicinal chemistry , pharmacology , biology , biochemistry , organic chemistry , physics , gene , quantum mechanics
The methyl group is one of the most commonly occurring carbon fragments in small‐molecule drugs. This simplest alkyl fragment appears in more than 67 % of the top‐selling drugs of 2011 and can modulate both the biological and physical properties of a molecule. This Review focuses on so‐called magic methyl effects on binding potency, where the seemingly mundane change of CH to CMe improves the IC 50 value of a drug candidate more than 100‐fold. This discussion is followed by a survey of recent advances in synthetic chemistry that allow the direct methylation of C(sp 2 )H and C(sp 3 )H bonds. It is our hope that the relevance of the meager methyl group to drug discovery as presented herein will inspire reports on new CH methylation reactions.