949902-59-4Relevant academic research and scientific papers
Discovery of N-substituted-endo-3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenol and -phenyl carboxamide series of μ-opioid receptor antagonists
Jiang, Lan,Beattie, David T.,Jacobsen, John R.,Kintz, Samuel,Obedencio, Glenmar P.,Saito, Daisuke,Stergiades, Ioanna,Vickery, Ross G.,Long, Daniel D.
, p. 2926 - 2930 (2017/06/05)
Gastrointestinal dysfunction as a consequence of the use of opioid analgesics is of significant clinical concern. First generation drugs to treat these opioid-induced side-effects were limited by their negative impact on opioid receptor agonist-induced analgesia. Second generation therapies target a localized, peripherally-restricted, non-CNS penetrant drug distribution of opioid receptor antagonists. Herein we describe the discovery of the N-substituted-endo-3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenol and -phenyl carboxamide series of μ-opioid receptor antagonists. This report highlights the discovery of the key μ-opioid receptor antagonist pharmacophore and the optimization of in vitro metabolic stability through the application of a phenol bioisostere. The compounds 27a and 31a with the most attractive in vitro profile, formed the basis for the application of Theravance Biopharma's multivalent approach to drug discovery to afford the clinical compound axelopran (TD-1211), targeted for the treatment of opioid-induced constipation.
Amidoalkyl-8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists
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Page/Page column 5; 11, (2009/04/24)
The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I): wherein R1, R2, R3, and a are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are antagonists at the mu opi
Disubstituted alkyl-8-azabicyclo[3.2.1] octane compounds as mu opioid receptor antagonists
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Page/Page column 12, (2009/04/24)
The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I): where the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are antagonists at the mu opioid receptor. The invention also provid
8-Azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists
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Page/Page column 21, (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.
