1. Nitrogen-bridged substituted 8-arylquinolines as potent PDE IV inhibitors
- Author
-
Patrick Lacombe, Denis Deschênes, Daniel Dubé, Laurence Dubé, Michel Gallant, Dwight Macdonald, Antony Mastracchio, Hélène Perrier, Stella Charleson, Zheng Huang, France Laliberté, Susana Liu, Joseph A. Mancini, Paul Masson, Myriam Salem, Angela Styhler, and Yves Girard
- Subjects
Stereochemistry ,medicine.drug_class ,Nitrogen ,Phosphodiesterase Inhibitors ,Clinical Biochemistry ,Pharmaceutical Science ,Biological Availability ,Carboxamide ,Biochemistry ,Chemical synthesis ,Sulfone ,Guinea pig ,chemistry.chemical_compound ,Pharmacokinetics ,In vivo ,Drug Discovery ,medicine ,Animals ,Molecular Biology ,Saimiri ,chemistry.chemical_classification ,biology ,Organic Chemistry ,Rats ,Enzyme ,chemistry ,Enzyme inhibitor ,biology.protein ,Quinolines ,Molecular Medicine ,Half-Life - 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.
- Published
- 2006