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The medicinal chemist's toolbox for late stage functionalization of drug-like molecules.
Cernak, Tim; Dykstra, Kevin D; Tyagarajan, Sriram; Vachal, Petr; Krska, Shane W.
Afiliación
  • Cernak T; Merck Research Laboratories, Discovery Chemistry - Automation & Capabilities Enhancement, 33 Avenue Louis Pasteur, BMB2-116B, Boston, Massachusetts 02115, USA. timothy_cernak@merck.com.
Chem Soc Rev ; 45(3): 546-76, 2016 Feb 07.
Article en En | MEDLINE | ID: mdl-26507237
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.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Chem Soc Rev Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Chem Soc Rev Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido