Alkyne-quinuclidine derivatives as potent and selective muscarinic antagonists for the treatment of COPD

Jean-Philippe Starck; Laurent Provins; Bernard Christophe; Michel Gillard; Sophie Jadot; Patrick Lo Brutto; Luc Quéré; Patrice Talaga; Michel Guyaux

doi:10.1016/j.bmcl.2008.03.024

Alkyne-quinuclidine derivatives as potent and selective muscarinic antagonists for the treatment of COPD

Bioorg Med Chem Lett. 2008 Apr 15;18(8):2675-8. doi: 10.1016/j.bmcl.2008.03.024. Epub 2008 Mar 18.

Authors

Jean-Philippe Starck¹, Laurent Provins, Bernard Christophe, Michel Gillard, Sophie Jadot, Patrick Lo Brutto, Luc Quéré, Patrice Talaga, Michel Guyaux

Affiliation

¹ UCB, R&D, Chemin du Foriest, B-1420 Braine-L'Alleud, Belgium.

PMID: 18359633
DOI: 10.1016/j.bmcl.2008.03.024

Abstract

SAR around alkyne-quinuclidine derivatives allowed the discovery of highly potent muscarinic antagonists displaying interesting preferential slow off-rates from the M3 receptor.

MeSH terms

Alkynes / chemistry*
Cholinergic Antagonists / chemistry
Molecular Structure
Muscarinic Antagonists / chemical synthesis*
Muscarinic Antagonists / chemistry
Muscarinic Antagonists / pharmacology*
Muscarinic Antagonists / therapeutic use
Pulmonary Disease, Chronic Obstructive / drug therapy*
Quinuclidines / chemical synthesis*
Quinuclidines / chemistry
Quinuclidines / pharmacology*
Quinuclidines / therapeutic use
Receptor, Muscarinic M2 / metabolism
Receptor, Muscarinic M3 / metabolism
Structure-Activity Relationship

Substances

Alkynes
Cholinergic Antagonists
Muscarinic Antagonists
Quinuclidines
Receptor, Muscarinic M2
Receptor, Muscarinic M3