3-Substituted 2-phenyl-indoles: Privileged structures for medicinal chemistry

Karl Henrik Johansson; T.B. Jørgensen; D.E. Gloriam; Hans Bräuner-Osborne; D.S. Pedersen

doi:10.1039/c2ra21902f

3-Substituted 2-phenyl-indoles: Privileged structures for medicinal chemistry

Karl Henrik Johansson, T.B. Jørgensen, D.E. Gloriam, Hans Bräuner-Osborne, D.S. Pedersen

49 Citations (Scopus)

Abstract

Privileged structures have been used in drug discovery targeting G protein-coupled receptors (GPCR) and other protein classes for more than 20 years. Their rich activity profiles and drug-like characteristics lend themselves to increased productivity in hit identification and lead optimisation. Recently we discovered two allosteric modulators 1 and 2 for the G protein-coupled receptor GPRC6A incorporating the privileged 2-phenyl-indole scaffold, functionalised at the 3-position. In order to develop new potential GPRC6A ligands we engaged in the development of synthetic routes to provide 2-phenyl-indoles with a variety of substituents at the indole 3-position. Herein we describe the development of optimised and efficient synthetic routes to a series of new 2-phenyl-indole building blocks 3 to 9 and show that these can be used to generate a broad variety of 3-substituted 2-phenyl-indoles of interest to medicinal chemists.

Original language	English
Journal	R S C Advances
Volume	3
Issue number	3
Pages (from-to)	945-960
ISSN	2046-2069
DOIs	https://doi.org/10.1039/c2ra21902f
Publication status	Published - 21 Jan 2013

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abstract = "Privileged structures have been used in drug discovery targeting G protein-coupled receptors (GPCR) and other protein classes for more than 20 years. Their rich activity profiles and drug-like characteristics lend themselves to increased productivity in hit identification and lead optimisation. Recently we discovered two allosteric modulators 1 and 2 for the G protein-coupled receptor GPRC6A incorporating the privileged 2-phenyl-indole scaffold, functionalised at the 3-position. In order to develop new potential GPRC6A ligands we engaged in the development of synthetic routes to provide 2-phenyl-indoles with a variety of substituents at the indole 3-position. Herein we describe the development of optimised and efficient synthetic routes to a series of new 2-phenyl-indole building blocks 3 to 9 and show that these can be used to generate a broad variety of 3-substituted 2-phenyl-indoles of interest to medicinal chemists.",

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T2 - Privileged structures for medicinal chemistry

AU - Johansson, Karl Henrik

AU - Jørgensen, T.B.

AU - Gloriam, D.E.

AU - Bräuner-Osborne, Hans

AU - Pedersen, D.S.

PY - 2013/1/21

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3-Substituted 2-phenyl-indoles: Privileged structures for medicinal chemistry

Abstract

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