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

TY - JOUR

T1 - 3-Substituted 2-phenyl-indoles

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

Y1 - 2013/1/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84870911301&partnerID=8YFLogxK

U2 - 10.1039/c2ra21902f

DO - 10.1039/c2ra21902f

M3 - Journal article

AN - SCOPUS:84870911301

SN - 2046-2069

VL - 3

SP - 945

EP - 960

JO - R S C Advances

JF - R S C Advances

IS - 3

ER -