title: Identification of novel series of human CCR1 antagonists.
abstract: 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.
authors.affiliation: Department of Chemistry, Tanabe Research Laboratories USA, Inc., 4540 Towne Centre Court, San Diego, CA 92121, USA.
authors.forename: Yun Feng
authors.initials: YF
authors.lastname: Xie
authors.forename: Ila
authors.initials: I
authors.lastname: Sircar
authors.forename: Kirk
authors.initials: K
authors.lastname: Lake
authors.forename: Mallareddy
authors.initials: M
authors.lastname: Komandla
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ligsay
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Kui
authors.initials: K
authors.lastname: Xu
authors.forename: Jason
authors.initials: J
authors.lastname: Parise
authors.forename: Lisa
authors.initials: L
authors.lastname: Schneider
authors.forename: Dingqiu
authors.initials: D
authors.lastname: Huang
authors.forename: Juping
authors.initials: J
authors.lastname: Liu
authors.forename: Naoki
authors.initials: N
authors.lastname: Sakurai
authors.forename: Miguel
authors.initials: M
authors.lastname: Barbosa
authors.forename: Rick
authors.initials: R
authors.lastname: Jack
mesh_terms: 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
chemical_list: C515429:CCL3 protein, human; D054405:Chemokine CCL3; D010880:Piperidines; D054389:Receptors, CCR1; C032727:piperidine; D002118:Calcium