Identification of novel series of human CCR1 antagonists.
A hit-to-lead optimization process was carried out on the high throughput screening hit compound 1 resulting in the identification of several potent and selective CCR1 receptor antagonists. Compound 37 shows the best overall profile with IC(50) values of <100 nM in binding and functional assays.
Xie
Yun Feng
YF
Department of Chemistry, Tanabe Research Laboratories USA, Inc., 4540 Towne Centre Court, San Diego, CA 92121, USA.
Sircar
Ila
I
Lake
Kirk
K
Komandla
Mallareddy
M
Ligsay
Kathleen
K
Li
Jian
J
Xu
Kui
K
Parise
Jason
J
Schneider
Lisa
L
Huang
Dingqiu
D
Liu
Juping
J
Sakurai
Naoki
N
Barbosa
Miguel
M
Jack
Rick
R
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D054405:Chemokine CCL3 / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C515429:CCL3 protein, human; D054405:Chemokine CCL3; D010880:Piperidines; D054389:Receptors, CCR1; C032727:piperidine; D002118:Calcium