Profound methyl effects in drug discovery and a call for new C-H methylation reactions.
Angew Chem Int Ed Engl
; 52(47): 12256-67, 2013 Nov 18.
Article
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| MEDLINE
| ID: mdl-24151256
ABSTRACT
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 â
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 CH methylation reactions.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Descubrimiento de Drogas
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2013
Tipo del documento:
Article