852435-98-4Relevant academic research and scientific papers
Development of synthetic routes, via a tropinone intermediate, to a long-acting muscarinic antagonist for the treatment of respiratory disease
Bream, Robert N.,Hayes, Doug,Hulcoop, David G.,Whiteman, Alexandra J.
, p. 641 - 650 (2013/06/27)
This contribution describes the development of two synthetic routes to an investigational muscarinic antagonist for the treatment of chronic obstructive pulmonary disease. The first route used a starting material which was in plentiful supply within the GSK network and was used to make material for early clinical trials and safety assessment studies. Further investigations identified a second, potential long-term manufacturing route from commercially available building blocks, using substrate control to install the two stereocentres with excellent selectivity. A key step was a substrate-directed epoxide reduction which also gave rise to a minor byproduct through a skeletal rearrangement of the tropane ring. A deuterium-labeling experiment was carried out, which shed light on the origin of the byproduct, and also guided the improvement of reaction conditions.
Design, synthesis and structure-activity relationship of N-substituted tropane muscarinic acetylcholine receptor antagonists
Lainé, Dramane I.,Yan, Hongxing,Xie, Haibo,Davis, Roderick S.,Dufour, Jeremy,Widdowson, Katherine L.,Palovich, Michael R.,Wan, Zehong,Foley, James J.,Schmidt, Dulcie B.,Hunsberger, Gerald E.,Burman, Miriam,Bacon, Alicia M.,Webb, Edward F.,Luttmann, Mark A.,Salmon, Michael,Sarau, Henry M.,Umbrecht, Sandra T.,Landis, Philip S.,Peck, Brian J.,Busch-Petersen, Jakob
scheme or table, p. 3366 - 3369 (2012/06/18)
A novel series of N-substituted tropane derivatives was characterized as potent muscarinic acetylcholine receptor antagonists (mAChRs). Kinetic washout studies showed that the N-endosubstituted analog 24 displayed much slower reversibility at mAChRs than
M3 MUSCARINIC ACETYLCHOLINE RECEPTOR ANTAGONISTS
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Page/Page column 29, (2008/06/13)
Muscarinic Acetylcholine receptor antagonists and methods of using them are provided.
