949902-42-5Relevant academic research and scientific papers
Discovery of Axelopran (TD-1211): A Peripherally Restricted μ-Opioid Receptor Antagonist
Armstrong, Scott R.,Beattie, David T.,Campbell, Christina B.,Church, Timothy J.,Colson, Pierre-Jean,Dalziel, Sean M.,Jacobsen, John R.,Jiang, Lan,Long, Daniel D.,Obedencio, Glenmar P.,Rapta, Miroslav,Saito, Daisuke,Stergiades, Ioanna,Tsuruda, Pamela R.,Van Dyke, Priscilla M.,Vickery, Ross G.
, (2019/12/11)
The effects of opioids in the central nervous system (CNS) provide significant benefit in the treatment of pain but can also lead to physical dependence and addiction, which has contributed to a growing opioid epidemic in the United States. Gastrointestinal dysfunction is an additional serious consequence of opioid use, and this can be treated with a localized drug distribution of a non-CNS penetrant, peripherally restricted opioid receptor antagonist. Herein, we describe the application of Theravance's multivalent approach to drug discovery coupled with a physicochemical property design strategy by which the N-substituted-endo-3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenyl carboxamide series of μ-opioid receptor antagonists was optimized to afford the orally absorbed, non-CNS penetrant, Phase 3 ready clinical compound axelopran (TD-1211) 19i as a potential treatment for opioid-induced constipation.
8-Azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists
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Page/Page column 18, (2008/06/13)
The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I): wherein R1, R2, R3, A, and G are defined in the specification, or a pharmaceutically-acceptable salt or solvate thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.
