Nitrogen-bridged substituted 8-arylquinolines as potent PDE IV inhibitors.
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.
Lacombe
Patrick
P
Merck Frosst Center for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Que., Canada H9R 4P8. patrick_lacombe@merck.com
Deschênes
Denis
D
Dubé
Daniel
D
Dubé
Laurence
L
Gallant
Michel
M
Macdonald
Dwight
D
Mastracchio
Antony
A
Perrier
Hélène
H
Charleson
Stella
S
Huang
Zheng
Z
Laliberté
France
F
Liu
Susana
S
Mancini
Joseph A
JA
Masson
Paul
P
Salem
Myriam
M
Styhler
Angela
A
Girard
Yves
Y
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
D010726:Phosphodiesterase Inhibitors; D011804:Quinolines; D009584:Nitrogen