title: Novel 2-aminooctahydrocyclopentalene-3a-carboxamides as potent CCR2 antagonists.
abstract: Novel CCR2 antagonists with a novel 2-aminooctahydrocyclopentalene-3a-carboxamide scaffold were designed. SAR studies led to a series of potent compounds. For example, compound 51 had a good PK profile in both dog and monkey, and exhibited excellent efficacy when dosed orally in an inflammation model in hCCR2 KI mice. In addition, an asymmetric synthesis to the core structures was developed.
authors.affiliation: Janssen Research and Development, LLC Welsh & McKean Roads, Spring House, Box 776, PA 19477, USA. ccai@its.jnj.com
authors.forename: Chaozhong
authors.initials: C
authors.lastname: Cai
authors.forename: Fu-An
authors.initials: FA
authors.lastname: Kang
authors.forename: Cuifen
authors.initials: C
authors.lastname: Hou
authors.forename: John C
authors.initials: JC
authors.lastname: O'Neill
authors.forename: Evan
authors.initials: E
authors.lastname: Opas
authors.forename: Sandra
authors.initials: S
authors.lastname: McKenney
authors.forename: Dana
authors.initials: D
authors.lastname: Johnson
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sui
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003517:Cyclopentanes / Q000737:chemistry*; D004195:Disease Models, Animal; D004285:Dogs; D006207:Half-Life; D000882:Haplorhini; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D011725:Pyridines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003517:Cyclopentanes; D011725:Pyridines; D054390:Receptors, CCR2; C024646:pentalenene