title: Identification and initial evaluation of 4-N-aryl-[1,4]diazepane ureas as potent CXCR3 antagonists.
abstract: The identification and evaluation of aryl-[1,4]diazepane ureas as functional antagonists of the chemokine receptor CXCR3 are described. Specific examples exhibit IC(50) values of approximately 60 nM in a calcium mobilization functional assay, and dose-dependently inhibit CXCR3 functional response to CXCL11 (interferon-inducible T-cell alpha chemoattractant/I-TAC) as measured by T-cell chemotaxis, with a potency of approximately 100 nM.
authors.affiliation: Pharmacopeia Drug Discovery, Inc., PO Box 5350, Princeton, NJ 08543, USA. acole@pcop.com
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Cole
authors.forename: Ilana L
authors.initials: IL
authors.lastname: Stroke
authors.forename: Marc-Raleigh
authors.initials: MR
authors.lastname: Brescia
authors.forename: Srilatha
authors.initials: S
authors.lastname: Simhadri
authors.forename: Joan J
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Zahid
authors.initials: Z
authors.lastname: Hussain
authors.forename: Michael
authors.initials: M
authors.lastname: Snider
authors.forename: Christopher
authors.initials: C
authors.lastname: Haskell
authors.forename: Sofia
authors.initials: S
authors.lastname: Ribeiro
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Appell
authors.forename: Ian
authors.initials: I
authors.lastname: Henderson
authors.forename: Maria L
authors.initials: ML
authors.lastname: Webb
mesh_terms: D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D054371:Chemokine CXCL11; D019743:Chemokines, CXC / Q000737:chemistry; D002633:Chemotaxis; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004583:Electrons; D006801:Humans; D007249:Inflammation; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000166:cytology; D014508:Urea / Q000737:chemistry*
chemical_list: C515202:CXCL11 protein, human; C515187:CXCR3 protein, human; D054371:Chemokine CXCL11; D019743:Chemokines, CXC; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D014508:Urea; D002118:Calcium