In vivo activity of an azole series of CCR2 antagonists

Chris A Smethurst; Nicola Bevan; Carl Brooks; Amanda Emmons; Peter J Gough; Claudette Mookherjee; Kitty Moores; Simon Peace; Joanne Philp; Val Piercy; Steve P Watson; Mara Zippoli

doi:10.1016/j.bmcl.2012.09.020

In vivo activity of an azole series of CCR2 antagonists

Bioorg Med Chem Lett. 2012 Dec 1;22(23):7252-5. doi: 10.1016/j.bmcl.2012.09.020. Epub 2012 Sep 23.

Authors

Chris A Smethurst¹, Nicola Bevan, Carl Brooks, Amanda Emmons, Peter J Gough, Claudette Mookherjee, Kitty Moores, Simon Peace, Joanne Philp, Val Piercy, Steve P Watson, Mara Zippoli

Affiliation

¹ GlaxoSmithKline Research and Development, Medicines Research Centre, Stevenage, UK.

PMID: 23079519
DOI: 10.1016/j.bmcl.2012.09.020

Abstract

Optimisation of a series of biaryl sulphonamides resulted in the identification of compound 14 [corrected] which demonstrated dose-dependent and strain-specific inhibition of monocyte recruitment in a thioglycollate-induced peritonitis model of inflammation. [Formula: see text]. [corrected].

MeSH terms

Administration, Oral
Animals
Azoles / chemical synthesis
Azoles / chemistry*
Azoles / pharmacokinetics
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System / metabolism
Half-Life
Protein Binding
Rats
Receptors, CCR2 / antagonists & inhibitors*
Receptors, CCR2 / metabolism
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry*
Sulfonamides / pharmacokinetics

Substances

Azoles
Cytochrome P-450 Enzyme Inhibitors
Receptors, CCR2
Sulfonamides
Cytochrome P-450 Enzyme System