Pyrrolo(iso)quinoline derivatives as 5-HT(2C) receptor agonists

David R Adams; Jonathan M Bentley; Karen R Benwell; Michael J Bickerdike; Corinna D Bodkin; Ian A Cliffe; Colin T Dourish; Ashley R George; Guy A Kennett; Antony R Knight; Craig S Malcolm; Howard L Mansell; Anil Misra; Kathleen Quirk; Jonathan R A Roffey; Steven P Vickers

doi:10.1016/j.bmcl.2005.10.029

Pyrrolo(iso)quinoline derivatives as 5-HT(2C) receptor agonists

Bioorg Med Chem Lett. 2006 Feb;16(3):677-80. doi: 10.1016/j.bmcl.2005.10.029. Epub 2005 Oct 27.

Authors

David R Adams¹, Jonathan M Bentley, Karen R Benwell, Michael J Bickerdike, Corinna D Bodkin, Ian A Cliffe, Colin T Dourish, Ashley R George, Guy A Kennett, Antony R Knight, Craig S Malcolm, Howard L Mansell, Anil Misra, Kathleen Quirk, Jonathan R A Roffey, Steven P Vickers

Affiliation

¹ Vernalis plc, Oakdene Court, 613 Reading Road, Winnersh, Wokingham, Berkshire RG41 5UA, UK.

PMID: 16257207
DOI: 10.1016/j.bmcl.2005.10.029

Abstract

A series of 1-(1-pyrrolo(iso)quinolinyl)-2-propylamines was synthesised and evaluated as 5-HT(2C) receptor agonists for the treatment of obesity. The general methods of synthesis of the precursor indoles are described. The functional efficacy and radioligand binding data for the compounds at 5-HT(2) receptor subtypes are reported. The analogue which showed the highest 5-HT(2C) binding affinity (27, 1.6nM) was found to be successful in reducing food intake in rats.

MeSH terms

Animals
Anti-Obesity Agents / pharmacology
Disease Models, Animal
Eating / drug effects*
Isoquinolines / chemistry
Isoquinolines / pharmacology*
Pyrroles / chemistry
Quinolines / chemistry
Quinolines / pharmacology*
Radioligand Assay
Rats
Serotonin 5-HT2 Receptor Agonists*
Serotonin Receptor Agonists / pharmacology*

Substances

Anti-Obesity Agents
Isoquinolines
Pyrroles
Quinolines
Serotonin 5-HT2 Receptor Agonists
Serotonin Receptor Agonists
isoquinoline