2-Mercaptoimidazoles, a new class of potent CCR2 antagonists.
We describe the synthesis and SAR of a new class of CCR2 antagonists based on 2-mercaptoimidazole scaffold. The initial lead 1a was optimized to the 3,4-disubstituted analogues 1p-(S) and 1q-(S), which have IC(50) values in the MCP-1 induced Ca-flux below 0.01 microM.
Van Lomen
Guy
G
Inflammation Research, Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium. gvlommen@prdbe.jnj.com
Doyon
Julien
J
Coesemans
Erwin
E
Boeckx
Staf
S
Cools
Marina
M
Buntinx
Mieke
M
Hermans
Bart
B
Van Wauwe
Jean
J
D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D018932:Chemokine CCL2 / Q000494:pharmacology; D005031:Ethylenethiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D007093:Imidazoles; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D005031:Ethylenethiourea; C077232:2-mercaptoimidazole