title: Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists.
abstract: A series of aniline-substituted tetrahydroquinoline C5a receptor antagonists were discovered. A functionality requirement of ortho substitution on the aniline was revealed. Secondary anilines, in general, outperformed tertiary analogs in inhibition of C5a-induced calcium mobilization. Further enhancement of activity was realized in the presence of an ortho hydroxyalkyl side chain. The functional IC(50) of selected analogs was optimized to the single-digit nanomolar level.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, Spring House, PA 19477-0776, USA. ygong@prdus.jnj.com
authors.forename: Yong
authors.initials: Y
authors.lastname: Gong
authors.forename: J Kent
authors.initials: JK
authors.lastname: Barbay
authors.forename: Mieke
authors.initials: M
authors.lastname: Buntinx
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Jean Van
authors.initials: JV
authors.lastname: Wauwe
authors.forename: Concha
authors.initials: C
authors.lastname: Claes
authors.forename: Guy Van
authors.initials: GV
authors.lastname: Lommen
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hornby
authors.forename: Wei
authors.initials: W
authors.lastname: He
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry*; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry*; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D008024:Ligands; D011804:Quinolines; D044087:Receptor, Anaphylatoxin C5a; C023650:aniline