Discovery of novel 8-azoniabicyclo[3.2.1]octane carbamates as muscarinic acetylcholine receptor antagonists.
In the course of our research program to develop novel muscarinic receptor antagonists for the treatment of COPD, new tropane carbamate derivatives were identified as potent anti-muscarinic agents. The synthesis, structure-activity relationships and pharmacological evaluation that led to the identification of compound 5o, are described.
Lainé
Dramane I
DI
GlaxoSmithkline, 709 Swedeland Road, King of Prussia, PA 19406, USA. dramane.i.laine@gsk.com
Xie
Haibo
H
Buffet
Noémie
N
Foley
James J
JJ
Buckley
Peter
P
Webb
Edward F
EF
Widdowson
Katherine L
KL
Palovich
Michael R
MR
Belmonte
Kristen E
KE
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D029424:Pulmonary Disease, Chronic Obstructive / Q000628:therapy; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014326:Tropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D001993:Bronchodilator Agents; D002219:Carbamates; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D014326:Tropanes