BIOMAT Database Logo BIOMAT Database Logo

Bioisosteric modification of salvinorin A, a potent and selective kappa-opioid receptor agonist. 2006

D Jeremy Stewart, and Hesham Fahmy, and Bryan L Roth, and Feng Yan, and Jordan K Zjawiony
Department of Pharmacognosy and National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677-1848, USA.

Salvinorin A ((2S,4aR,6aR,7R,9S,10aS, 10bR)-2H-naphtho[2,1-c]pyran-7-carboxylic acid, 9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo methyl ester, 1, CAS 83729-01-5) has been shown to bind with high affinity and selectivity to the kappa-opioid receptor (KOR) as an agonist. Bioisosteres of 1 were developed and biologically evaluated in binding and functional assays. The C-2 thioacetate isoster produced comparable activity to 1, but nitrogen substitution had a diminishing effect. Intermediates, which lack a beta-carbonyl at C-2, displayed moderate affinity. The derivatives were tested against all opioid subtypes and were selective towards KOR.

UI MeSH Term Description Entries
D007202 Indicators and Reagents Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499) Indicator,Reagent,Reagents,Indicators,Reagents and Indicators
D007536 Isomerism The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Isomerisms
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D011619 Psychotropic Drugs A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). Psychoactive Agent,Psychoactive Agents,Psychoactive Drug,Psychopharmaceutical,Psychopharmaceuticals,Psychotropic Drug,Psychoactive Drugs,Agent, Psychoactive,Agents, Psychoactive,Drug, Psychoactive,Drug, Psychotropic,Drugs, Psychoactive,Drugs, Psychotropic
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004224 Diterpenes Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate. Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding
D013055 Spectrophotometry, Infrared Spectrophotometry in the infrared region, usually for the purpose of chemical analysis through measurement of absorption spectra associated with rotational and vibrational energy levels of molecules. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) IR Spectra,Infrared Spectrophotometry,IR Spectras,Spectra, IR

Related Publications

D Jeremy Stewart, and Hesham Fahmy, and Bryan L Roth, and Feng Yan, and Jordan K Zjawiony
Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist.
September 2002, Proceedings of the National Academy of Sciences of the United States of America,
D Jeremy Stewart, and Hesham Fahmy, and Bryan L Roth, and Feng Yan, and Jordan K Zjawiony
Asymmetric synthesis of salvinorin A, a potent kappa opioid receptor agonist.
July 2007, Journal of the American Chemical Society,
D Jeremy Stewart, and Hesham Fahmy, and Bryan L Roth, and Feng Yan, and Jordan K Zjawiony
Salvinorin A: a novel and highly selective kappa-opioid receptor agonist.
October 2004, Life sciences,
D Jeremy Stewart, and Hesham Fahmy, and Bryan L Roth, and Feng Yan, and Jordan K Zjawiony
Studies toward the pharmacophore of salvinorin A, a potent kappa opioid receptor agonist.
January 2005, Journal of medicinal chemistry,
D Jeremy Stewart, and Hesham Fahmy, and Bryan L Roth, and Feng Yan, and Jordan K Zjawiony
N-methylacetamide analog of salvinorin A: a highly potent and selective kappa-opioid receptor agonist with oral efficacy.
January 2008, The Journal of pharmacology and experimental therapeutics,
D Jeremy Stewart, and Hesham Fahmy, and Bryan L Roth, and Feng Yan, and Jordan K Zjawiony
Modification of the furan ring of salvinorin A: identification of a selective partial agonist at the kappa opioid receptor.
February 2009, Bioorganic & medicinal chemistry,
D Jeremy Stewart, and Hesham Fahmy, and Bryan L Roth, and Feng Yan, and Jordan K Zjawiony
2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A.
March 2008, The Journal of pharmacology and experimental therapeutics,
D Jeremy Stewart, and Hesham Fahmy, and Bryan L Roth, and Feng Yan, and Jordan K Zjawiony
A unique natural selective kappa-opioid receptor agonist, salvinorin A, and its roles in human therapeutics.
May 2017, Phytochemistry,
D Jeremy Stewart, and Hesham Fahmy, and Bryan L Roth, and Feng Yan, and Jordan K Zjawiony
Kappa-opioid receptor-selective dicarboxylic ester-derived salvinorin A ligands.
May 2013, Bioorganic & medicinal chemistry letters,
D Jeremy Stewart, and Hesham Fahmy, and Bryan L Roth, and Feng Yan, and Jordan K Zjawiony
Antinociceptive profile of salvinorin A, a structurally unique kappa opioid receptor agonist.
January 2006, Pharmacology, biochemistry, and behavior,
Copied contents to your clipboard!