Identification of a sulfonamide series of CCR2 antagonists

Simon Peace; Joanne Philp; Carl Brooks; Val Piercy; Kitty Moores; Chris Smethurst; Steve Watson; Simon Gaines; Mara Zippoli; Claudette Mookherjee; Robert Ife

doi:10.1016/j.bmcl.2010.04.142

Identification of a sulfonamide series of CCR2 antagonists

Bioorg Med Chem Lett. 2010 Jul 1;20(13):3961-4. doi: 10.1016/j.bmcl.2010.04.142. Epub 2010 May 7.

Authors

Simon Peace¹, Joanne Philp, Carl Brooks, Val Piercy, Kitty Moores, Chris Smethurst, Steve Watson, Simon Gaines, Mara Zippoli, Claudette Mookherjee, Robert Ife

Affiliation

¹ GlaxoSmithKline Medicines Research Centre, Stevenage, UK. Simon.2.Peace@gsk.com

PMID: 20627722
DOI: 10.1016/j.bmcl.2010.04.142

Abstract

A series of sulfonamide CCR2 antagonists was identified by high-throughput screening. Management of molecular weight and physical properties, in particular moderation of lipophilicity and study of pK(a), yielded highly potent CCR2 antagonists exhibiting good pharmacokinetic properties and improved potency in the presence of human plasma.

MeSH terms

Animals
Dose-Response Relationship, Drug
High-Throughput Screening Assays
Humans
Mice
Molecular Structure
Receptors, CCR1 / antagonists & inhibitors
Receptors, CCR2 / antagonists & inhibitors*
Stereoisomerism
Structure-Activity Relationship
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Receptors, CCR1
Receptors, CCR2
Sulfonamides