title: Nitrogen-bridged substituted 8-arylquinolines as potent PDE IV inhibitors.
abstract: Potent inhibitors of the human PDE IV enzyme are described. Substituted 8-arylquinoline analogs bearing nitrogen-linked side chain were identified as potent inhibitors based on the SAR described herein. The pharmacokinetic profile of the best analog and the in vivo efficacy in an ovalbumin-induced bronchoconstriction assay in conscious guinea pigs are reported.
authors.affiliation: Merck Frosst Center for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Que., Canada H9R 4P8. patrick_lacombe@merck.com
authors.forename: Patrick
authors.initials: P
authors.lastname: Lacombe
authors.forename: Denis
authors.initials: D
authors.lastname: Deschênes
authors.forename: Daniel
authors.initials: D
authors.lastname: Dubé
authors.forename: Laurence
authors.initials: L
authors.lastname: Dubé
authors.forename: Michel
authors.initials: M
authors.lastname: Gallant
authors.forename: Dwight
authors.initials: D
authors.lastname: Macdonald
authors.forename: Antony
authors.initials: A
authors.lastname: Mastracchio
authors.forename: Hélène
authors.initials: H
authors.lastname: Perrier
authors.forename: Stella
authors.initials: S
authors.lastname: Charleson
authors.forename: Zheng
authors.initials: Z
authors.lastname: Huang
authors.forename: France
authors.initials: F
authors.lastname: Laliberté
authors.forename: Susana
authors.initials: S
authors.lastname: Liu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Mancini
authors.forename: Paul
authors.initials: P
authors.lastname: Masson
authors.forename: Myriam
authors.initials: M
authors.lastname: Salem
authors.forename: Angela
authors.initials: A
authors.lastname: Styhler
authors.forename: Yves
authors.initials: Y
authors.lastname: Girard
mesh_terms: D000818:Animals; D001682:Biological Availability; D006207:Half-Life; D009584:Nitrogen / Q000737:chemistry*; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D012453:Saimiri
chemical_list: D010726:Phosphodiesterase Inhibitors; D011804:Quinolines; D009584:Nitrogen