Profound Methyl Effects in Drug Discovery and a Call for New CH Methylation Reactions. Issue 47 (22nd October 2013)

• Record Type: Journal Article
• Authors: Schönherr, Heike; Cernak, Tim
• Is Part Of: Angewandte Chemie international edition. Volume 52:Issue 47(2013)
• Page Start: 12256
• Page End: 12267
• Publication Date: 2013-10-22
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201303207
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 CH to CMe improves the IC₅₀ 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(sp²)H and C(sp³)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 CH methylation reactions.</p> </abstract>