title: 3-Amino-1-alkyl-cyclopentane carboxamides as small molecule antagonists of the human and murine CC chemokine receptor 2.
abstract: A series of low molecular weight antagonists of both the human and murine CC chemokine receptor 2, containing a 1-alkyl-3-(3-methyl-4-spiroindenylpiperidine)-substituted cyclopentanecarboxamide, is described. A SAR study of the C(1) substituent revealed that short, branched alkyl groups such as isopropyl, isobutyl, or cyclopropyl are optimal for both human and murine CCR2 binding activity.
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065, USA. gabor_butora@merck.com <gabor_butora@merck.com>
authors.forename: Gabor
authors.initials: G
authors.lastname: Butora
authors.forename: Richard
authors.initials: R
authors.lastname: Jiao
authors.forename: William H
authors.initials: WH
authors.lastname: Parsons
authors.forename: Pasquale P
authors.initials: PP
authors.lastname: Vicario
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Julia M
authors.initials: JM
authors.lastname: Ayala
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Cascieri
authors.forename: Lihu
authors.initials: L
authors.lastname: Yang
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry*; D000818:Animals; D002244:Carbon / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; C515334:CCR2 protein, human; C515335:Ccr2 protein, mouse; C515336:Ccr2 protein, rat; D003517:Cyclopentanes; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C502584:cyclopentane dicarboxamide; D002244:Carbon