Nitrogen-bridged substituted 8-arylquinolines as potent PDE IV inhibitors

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; Yves Girard

doi:10.1016/j.bmcl.2006.02.043

Nitrogen-bridged substituted 8-arylquinolines as potent PDE IV inhibitors

Bioorg Med Chem Lett. 2006 May 15;16(10):2608-12. doi: 10.1016/j.bmcl.2006.02.043. Epub 2006 Mar 3.

Authors

Patrick Lacombe¹, 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, Yves Girard

Affiliation

¹ Merck Frosst Center for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Que., Canada H9R 4P8. patrick_lacombe@merck.com

PMID: 16516471
DOI: 10.1016/j.bmcl.2006.02.043

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.

MeSH terms

Animals
Biological Availability
Half-Life
Nitrogen / chemistry*
Phosphodiesterase Inhibitors / chemistry*
Phosphodiesterase Inhibitors / pharmacokinetics
Phosphodiesterase Inhibitors / pharmacology*
Quinolines / chemistry*
Quinolines / pharmacokinetics
Quinolines / pharmacology*
Rats
Saimiri

Substances

Phosphodiesterase Inhibitors
Quinolines
Nitrogen