title: Discovery and SAR of 5-aminooctahydrocyclopentapyrrole-3a-carboxamides as potent CCR2 antagonists.
abstract: SAR study of 5-aminooctahydrocyclopentapyrrole-3a-carboxamide scaffold led to identification of several CCR2 antagonists with potent activity in both binding and functional assays. Their cardiovascular safety and pharmacokinetic properties were also evaluated.
authors.affiliation: Janssen Research and Development, L.L.C. Welsh & McKean Roads, Spring House, Box 776, PA 19477, USA. Electronic address: ccai@its.jnj.com.
authors.forename: Chaozhong
authors.initials: C
authors.lastname: Cai
authors.affiliation: Janssen Research and Development, L.L.C. Welsh & McKean Roads, Spring House, Box 776, PA 19477, USA.
authors.forename: Dave F
authors.initials: DF
authors.lastname: McComsey
authors.affiliation: Janssen Research and Development, L.L.C. Welsh & McKean Roads, Spring House, Box 776, PA 19477, USA.
authors.forename: Cuifen
authors.initials: C
authors.lastname: Hou
authors.affiliation: Janssen Research and Development, L.L.C. Welsh & McKean Roads, Spring House, Box 776, PA 19477, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: O'Neill
authors.affiliation: Janssen Research and Development, L.L.C. Welsh & McKean Roads, Spring House, Box 776, PA 19477, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Opas
authors.affiliation: Janssen Research and Development, L.L.C. Welsh & McKean Roads, Spring House, Box 776, PA 19477, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: McKenney
authors.affiliation: Janssen Research and Development, L.L.C. Welsh & McKean Roads, Spring House, Box 776, PA 19477, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Johnson
authors.affiliation: Janssen Research and Development, L.L.C. Welsh & McKean Roads, Spring House, Box 776, PA 19477, USA.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sui
mesh_terms: D003517:Cyclopentanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D008968:Molecular Conformation; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C000592171:5-aminooctahydrocyclopentapyrrole-3a-carboxamide; C515334:CCR2 protein, human; D003517:Cyclopentanes; D011758:Pyrroles; D054390:Receptors, CCR2
keywords: 1,3-Dipolar cycloaddition; CCR2 antagonist; Carbamate; Optimization