The medicinal chemist's toolbox for late stage functionalization of drug-like molecules.
Chem Soc Rev
; 45(3): 546-76, 2016 Feb 07.
Article
em En
| MEDLINE
| ID: mdl-26507237
ABSTRACT
The advent of modern C-H functionalization chemistries has enabled medicinal chemists to consider a synthetic strategy, late stage functionalization (LSF), which utilizes the C-H bonds of drug leads as points of diversification for generating new analogs. LSF approaches offer the promise of rapid exploration of structure activity relationships (SAR), the generation of oxidized metabolites, the blocking of metabolic hot spots and the preparation of biological probes. This review details a toolbox of intermolecular C-H functionalization chemistries with proven applicability to drug-like molecules, classified by regioselectivity patterns, and gives guidance on how to systematically develop LSF strategies using these patterns and other considerations. In addition, a number of examples illustrate how LSF approaches have been used to impact actual drug discovery and chemical biology efforts.
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Bases de dados:
MEDLINE
Idioma:
En
Revista:
Chem Soc Rev
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos