Diaryl substituted pyrazoles as potent CCR2 receptor antagonists

Anthony B Pinkerton; Dehua Huang; Rowena V Cube; John H Hutchinson; Mary Struthers; Julia M Ayala; Pasquale P Vicario; Sima R Patel; Thomas Wisniewski; Julie A DeMartino; Jean-Michel Vernier

doi:10.1016/j.bmcl.2006.10.060

Diaryl substituted pyrazoles as potent CCR2 receptor antagonists

Bioorg Med Chem Lett. 2007 Feb 1;17(3):807-13. doi: 10.1016/j.bmcl.2006.10.060. Epub 2006 Oct 25.

Authors

Anthony B Pinkerton¹, Dehua Huang, Rowena V Cube, John H Hutchinson, Mary Struthers, Julia M Ayala, Pasquale P Vicario, Sima R Patel, Thomas Wisniewski, Julie A DeMartino, Jean-Michel Vernier

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. apinkerton@kalypsys.com

PMID: 17088058
DOI: 10.1016/j.bmcl.2006.10.060

Abstract

We have identified and synthesized a series of diaryl substituted pyrazoles as potent antagonists of the chemokine receptor subtype 2. Structure-activity relationship studies directed toward improving the potency led to the discovery of 23 (IC50 = 6 nM).

MeSH terms

Chemotaxis / drug effects
Humans
In Vitro Techniques
Indicators and Reagents
Monocytes / drug effects
Oxidation-Reduction
Pyrazoles / chemical synthesis*
Pyrazoles / pharmacology*
Receptors, CCR2
Receptors, Chemokine / antagonists & inhibitors*
Receptors, Chemokine / drug effects
Structure-Activity Relationship

Substances

CCR2 protein, human
Indicators and Reagents
Pyrazoles
Receptors, CCR2
Receptors, Chemokine