Discovery of a novel indole series of EP1 receptor antagonists by scaffold hopping

Adrian Hall; Andy Billinton; Susan H Brown; Anita Chowdhury; Gerard M P Giblin; Paul Goldsmith; David N Hurst; Alan Naylor; Sadhana Patel; Tiziana Scoccitti; Pamela J Theobald

doi:10.1016/j.bmcl.2008.03.018

Discovery of a novel indole series of EP1 receptor antagonists by scaffold hopping

Bioorg Med Chem Lett. 2008 Apr 15;18(8):2684-90. doi: 10.1016/j.bmcl.2008.03.018. Epub 2008 Mar 10.

Authors

Adrian Hall¹, Andy Billinton, Susan H Brown, Anita Chowdhury, Gerard M P Giblin, Paul Goldsmith, David N Hurst, Alan Naylor, Sadhana Patel, Tiziana Scoccitti, Pamela J Theobald

Affiliation

¹ Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom. adrian.2.hall@gsk.com

PMID: 18378447
DOI: 10.1016/j.bmcl.2008.03.018

Abstract

We describe the medicinal chemistry approach that generated a novel indole series of EP(1) receptor antagonists. The SAR of this new template was evaluated and culminated in the identification of compound 12g which demonstrated in vivo efficacy in a preclinical model of inflammatory pain.

MeSH terms

Animals
Humans
Hydrogen Bonding
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology*
Microsomes, Liver / drug effects
Microsomes, Liver / metabolism
Models, Molecular
Molecular Structure
Rats
Receptors, Prostaglandin E / antagonists & inhibitors*
Receptors, Prostaglandin E / metabolism*
Receptors, Prostaglandin E, EP1 Subtype
Structure-Activity Relationship
Thiazoles / chemistry

Substances

Indoles
PTGER1 protein, human
Receptors, Prostaglandin E
Receptors, Prostaglandin E, EP1 Subtype
Thiazoles
indole