Potent achiral agonists of the growth hormone secretagogue (ghrelin) receptor. Part 2: Lead optimisation

Jason Witherington; Lee Abberley; Michael A Briggs; Katharine Collis; David K Dean; Alessandra Gaiba; N Paul King; Helmut Kraus; Nicola Shuker; Jon G A Steadman; Andrew K Takle; Gareth Sanger; Graham Wadsworth; Sharon Butler; Fiona McKay; Alison Muir; Kim Winborn; Tom D Heightman

doi:10.1016/j.bmcl.2007.12.021

Potent achiral agonists of the growth hormone secretagogue (ghrelin) receptor. Part 2: Lead optimisation

Bioorg Med Chem Lett. 2008 Mar 15;18(6):2203-5. doi: 10.1016/j.bmcl.2007.12.021. Epub 2007 Dec 15.

Authors

Jason Witherington¹, Lee Abberley, Michael A Briggs, Katharine Collis, David K Dean, Alessandra Gaiba, N Paul King, Helmut Kraus, Nicola Shuker, Jon G A Steadman, Andrew K Takle, Gareth Sanger, Graham Wadsworth, Sharon Butler, Fiona McKay, Alison Muir, Kim Winborn, Tom D Heightman

Affiliation

¹ Department of Medicinal Chemistry & DMPK, Neurology & GI Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. Jason_Witherington@GSK.com

PMID: 18316188
DOI: 10.1016/j.bmcl.2007.12.021

Abstract

A series of small molecule orally bioavailable ghrelin receptor agonists have been identified through systematic optimisation of a high throughput screening hit.

MeSH terms

Administration, Oral
Animals
Biological Availability
Fluorescence
Indoles / chemical synthesis
Indoles / pharmacology*
Male
Molecular Structure
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1B / metabolism
Receptors, Ghrelin / agonists*
Receptors, Ghrelin / metabolism
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / pharmacology*

Substances

Indoles
Receptor, Serotonin, 5-HT1B
Receptors, Ghrelin
SB-791016
Sulfonamides