Diaryl substituted pyrazoles as potent CCR2 receptor antagonists.
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).
Pinkerton
Anthony B
AB
Department of Medicinal Chemistry, Merck Research Laboratories, MRLSDB2, 3535 General Atomics Court, San Diego, CA 92121, USA. apinkerton@kalypsys.com
Huang
Dehua
D
Cube
Rowena V
RV
Hutchinson
John H
JH
Struthers
Mary
M
Ayala
Julia M
JM
Vicario
Pasquale P
PP
Patel
Sima R
SR
Wisniewski
Thomas
T
DeMartino
Julie A
JA
Vernier
Jean-Michel
JM
D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009000:Monocytes / Q000187:drug effects; D010084:Oxidation-Reduction; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000187:drug effects; D013329:Structure-Activity Relationship
C515334:CCR2 protein, human; D007202:Indicators and Reagents; D011720:Pyrazoles; D054390:Receptors, CCR2; D019707:Receptors, Chemokine