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Funcionalizaciones divergentes de C-H dirigidas por farmacóforos de sulfonamidas: diversificación en etapa tardía

Hui-Xiong Dai¹, Antonia F Stepan, Mark S Plummer

¹Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

Journal of the American Chemical Society

|April 15, 2011

Resumen

Las sulfonamidas permiten la diversificación de fármacos en etapas tardías a través de la funcionalización C-H. Este enfoque permite la síntesis rápida de nuevos análogos de fármacos, como los potenciales inhibidores de la ciclooxigenasa-II, a partir de fármacos candidatos existentes.

Área de la Ciencia:

Química Medicinal La Química Medicinal es un campo de estudio que abarca la Química Medicinal.
Síntesis orgánica La síntesis orgánica.
Descubrimiento de Drogas Descubrimiento de Drogas

Sus antecedentes:

El descubrimiento de fármacos se basa en la identificación de compuestos de plomo y la síntesis de análogos.
Los farmacóforos comunes pueden dirigir la funcionalización C-H para una síntesis analógica eficiente.
Las sulfonamidas son farmacóforos prevalentes en los medicamentos comercializados, incluido el celecoxib.

Objetivo del estudio:

Demostrar la diversificación en etapa tardía de las sulfonamidas a través de la funcionalización C-H divergente.
Desarrollar un conjunto versátil de reacciones de funcionalización C-H para las sulfonamidas.
Para sintetizar nuevos análogos de fármacos, específicamente potenciales inhibidores de la ciclooxigenasa-II.

Principales métodos:

Desarrolló seis reacciones distintas de funcionalización C-H de la sulfonamida: olefinación, arilación, alquilación, halogenación, carboxilación y carbonilación.
Utilizó una estrategia de grupo de dirección de sulfonamidas para la funcionalización selectiva del sitio C-H.
Se aplicó la diversificación en etapa tardía a un fármaco candidato a la sulfonamida.

Principales resultados:

Se ha demostrado con éxito la funcionalización C-H divergente de las sulfonamidas.
Sintetizó nuevos análogos de celecoxib como potenciales inhibidores de la ciclooxigenasa-II.
Las sulfonamidas establecidas como grupos directivos efectivos para la activación de C-H.

Conclusiones:

La diversificación en etapa tardía a través de la funcionalización C-H de la sulfonamida es una estrategia viable para el descubrimiento de fármacos.
Los métodos desarrollados ofrecen una amplia utilidad para la síntesis de diversos análogos de drogas.
Los grupos de dirección de sulfonamidas son efectivos en la activación de C-H, lo que refleja los éxitos en la catálisis asimétrica.

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