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Discovery of biphenyl piperazines as novel and long acting muscarinic acetylcholine receptor antagonists.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2008 Oct 09; Vol. 51 (19), pp. 5915-8. Date of Electronic Publication: 2008 Sep 18. - Publication Year :
- 2008
-
Abstract
- A series of novel biphenyl piperazines was discovered as highly potent muscarinic acetylcholine receptor antagonists via high throughput screening and subsequent optimization. Compound 5c with respective 500- and 20-fold subtype selectivity for M3 over M2 and M1 exhibited excellent inhibitory activity and long duration of action in a bronchoconstriction in vivo model in mice via intranasal administration. The novel inhaled mAChR antagonists are potentially useful therapeutic agents for the treatment of chronic obstructive pulmonary disease.
- Subjects :
- Administration, Intranasal
Animals
Bronchial Provocation Tests
Bronchoconstrictor Agents pharmacology
Bronchodilator Agents chemical synthesis
Bronchodilator Agents chemistry
Disease Models, Animal
Drug Evaluation, Preclinical
Methacholine Chloride pharmacology
Mice
Molecular Structure
Piperazines chemical synthesis
Piperazines chemistry
Stereoisomerism
Structure-Activity Relationship
Bronchoconstriction drug effects
Bronchodilator Agents pharmacology
Piperazines pharmacology
Receptors, Muscarinic drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 51
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18798607
- Full Text :
- https://doi.org/10.1021/jm800935u