141555-34-2Relevant academic research and scientific papers
Design, synthesis, and preliminary evaluation of a potential synthetic opioid rescue agent
Baynard, Caroline,Butelman, Eduardo R.,Hedrick, Sidnee L.,Horn, Jamie,Jackson, Karen,Kaska, Sophia,Kreek, Mary Jeanne,Leggas, Markos,Luo, Dan,Niloy, Kumar Kulldeep,Prisinzano, Thomas E.,Sarma, Rupam
, (2021/09/14)
Background: One of the most prominent opioid analgesics in the United States is the high potency agonist fentanyl. It is used in the treatment of acute and chronic pain and as an anesthetic adjuvant. When used inappropriately, however, ingestion of just a
Compounds including Cox inhibitor moiety and enhanced delivery of active drugs using same
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, (2017/05/06)
The presently-disclosed subject matter includes compounds including a cyclooxygenase enzyme inhibitor moiety and a moiety derived from a drug of interest. In some embodiments, the drug of interest is an opioid. In some embodiments, the compound includes a diclofenac moiety and a naltrexone or naltrexol moiety. The compounds allow for enhanced delivery rates across skin.
Optimization of naltrexone diclofenac codrugs for sustained drug delivery across microneedle-treated skin
Ghosh, Priyanka,Lee, Domin,Kim, Kyung Bo,Stinchcomb, Audra L.
, p. 148 - 159 (2014/01/17)
Purpose: The purpose of this work was to optimize the structure of codrugs for extended delivery across microneedle treated skin. Naltrexone, the model compound was linked with diclofenac, a nonspecific cyclooxygenase inhibitor to enhance the pore lifetim
An efficient synthesis of 3-OBn-6β,14-epoxy-bridged opiates from naltrexone and identification of a related dual MOR inverse agonist/KOR agonist
Martin, David J.,Fitzmorris, Paul E.,Deveau, Amy M.,Li, Bo,Ayestas, Mario,Sally, Ellicott J.,Dersch, Christina M.,Rothman, Richard B.
, p. 6801 - 6805,5 (2020/09/02)
In an effort to better understand the conformational preferences that inform the biological activity of naltrexone and related naltrexol derivatives, a new synthesis of the restricted analog 3-OBn-6β,14-epoxymorphinan 4 is described. 4 was synthesized starting from naltrexone in 50% overall yield, proceeding through the OBn-6α-triflate intermediate 8. Key steps to the synthesis include benzylation (96% yield), reduction (90% yield, α:β:3:2), followed by a one-pot triflation/displacement sequence (96% yield) to yield the desired bridged epoxy derivative 4. X-ray crystallographic analysis of intermediate 3-OBn-6α-naltrexol 7a supports population of the key boat conformation required for the epoxy ring closure. We also report that the 6β-mesylate 10-a high affinity opioid receptor ligand, the epimeric derivative of 11, and an analog of 12-functions as an inverse agonist at the mu opioid receptor using herkinorin pre-conditioned cells and an agonist at the kappa opioid receptor when evaluated in independent in vitro [ 35S]-GTP-γ-S assays.
Design, synthesis, and characterization of 6β-naltrexol analogs, and their selectivity for in vitro opioid receptor subtypes
Pelotte, Andrea L.,Smith, Ryan M.,Ayestas, Mario,Dersch, Christina M.,Bilsky, Edward J.,Rothman, Richard B.,Deveau, Amy M.
supporting information; experimental part, p. 2811 - 2814 (2010/01/16)
Since the mu opioid receptor (MOR) is known to be involved in the therapeutically relevant pathways leading to the manifestation of pain and addiction, we are currently studying the specific structural characteristics that promote antagonism at the MOR. T
N-OXIDES OF 4,5-EPOXY-MORPHINANIUM ANALOGS
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Page/Page column 104, (2009/06/27)
Novel N-oxides of 4,5-epoxy-morphinanIum analogs are disclosed. Pharmaceutical compositions containing the N-oxides of 4,5-epoxy-morphinanium analogs and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as modulators of opioid receptors.
N-OXIDES OF 4,5-EPOXY-MORPHINANIUM ANALOGS
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Page/Page column 102, (2008/12/06)
Novel N-oxides of 4,5-epoxy-morphinanium analogs are disclosed. Pharmaceutical compositions containing the N-oxides of 4,5-epoxy-morphinanium analogs and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as modulators of opioid receptors.
Electrophilic opioid ligands. Oxygen tethered α-methylene-γ-lactone, acrylate, isothiocyanate, and epoxide derivatives of 6β-naltrexol
Dasher,Klein,Nelson
, p. 2374 - 2384 (2007/10/02)
O6-Ether derivatives of 6β-naltrexol in which the ether substituent includes various electrophilic groups have been synthesized in an effort to examine structure-activity requirements at the 6β-substituent for receptor affinity and irreversibil
