A5086184066- Neuropeptides and Animal Physiology
- Synthesis of Organic Compounds
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Synthesis and Biological Evaluation
- Pharmacological Receptor Mechanisms and Effects
- Chemical synthesis and alkaloids
- Chemical Reaction Mechanisms
- Bioactive natural compounds
- Gastrointestinal motility and disorders
- Receptor Mechanisms and Signaling
- Phenothiazines and Benzothiazines Synthesis and Activities
- Alkaloids: synthesis and pharmacology
- Nanofabrication and Lithography Techniques
- Oxidative Organic Chemistry Reactions
- Peptidase Inhibition and Analysis
- Chemical synthesis and pharmacological studies
- Various Chemistry Research Topics
- Organophosphorus compounds synthesis
- Marine Sponges and Natural Products
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Molecular Junctions and Nanostructures
- History and advancements in chemistry
- Pharmacological Effects and Toxicity Studies
- Phosphorus compounds and reactions
- Synthesis and Reactions of Organic Compounds
Kalamazoo College
2020
Virginia Commonwealth University
2013-2019
University of Lynchburg
2011-2013
University of Stirling
1971-1974
μ opioid receptor (MOR) agonists have been widely applied for treating moderate to severe pain. However, numerous adverse effects associated with their application, including opioid-induced constipation (OIC), respiratory depression, and addiction. On the basis of previous work in our laboratory, NAP, a 6β-N-4′-pyridyl substituted naltrexamine derivative, was identified as peripheral MOR antagonist that may be used treat OIC. To further explore its structure–activity relationship, new series...
Mounting evidence has suggested that G protein-coupled receptors can be stabilized in multiple conformations response to distinct ligands, which exert discrete functions through selective activation of various downstream signaling events. In accordance with this concept, we report biased one C6-heterocyclic substituted naltrexamine derivative, namely, 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(4′-pyridylcarboxamido)morphinan (NAP) at the mu opioid receptor (MOR). NAP acted as a low...
The involvement of the neurotransmitter serotonin (5-HT) in numerous physiological functions is often attributed to diversity receptors with which it interacts. Ligands targeting receptor 2B (5-HT2B) have received renewed interest for their potential help understand role 5-HT2B migraines, drug abuse, neurodegenerative diseases, and irritable bowel syndrome. To date, most ligands been nitrogen-containing compounds. natural product 5-hydroxy-2-(2-phenylethyl)chromone (5-HPEC, 5) has shown...
The 6β-N-heterocyclic naltrexamine derivative, NAP, has been demonstrated to be a peripherally selective mu opioid receptor modulator. To further improve peripheral selectivity of this highly potent ligand, its pyridal ring was quaterinized with benzyl bromide produce BNAP. In radioligand binding assay, the Ki BNAP for MOR 0.76 ± 0.09 nM and >900-fold more than DOR. KOR 3.46 0.05 nM. [35S]GTPγS ligand stimulated showed low agonist efficacy 14.6% maximum response DAMGO an EC50 4.84 0.6...
The synthesis and characterization of novel N-arylhydroxylamine-based molecular wires are described for use in the site-directed covalent immobilization whole IgG antibodies onto gold electrode surfaces. hydroxylamine, electrochemically generated situ from reduction corresponding nitrobenzene, is stable under a wide range solution conditions reacts selectively with carbohydrate away antibody-binding site to allow development immunosensors maximal activity. Cyclic voltammetric responses have...
Opioids are the mainstay for cancer and noncancer pain management. However, their use is often associated with multiple adverse effects. Among them, most common persistent one probably opioid-induced constipation (OIC). Periphery selective opioid antagonists may alleviate symptoms of OIC without compromising analgesic effects opioids. Recently our laboratories have identified novel lead compound, 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4′-pyridyl)acetamido]morphinan (NAP), as a...
Activation of μ‐opioid receptors (MORs) on enteric neurons during opioid treatment inhibits gastrointestinal peristalsis and leads to constipation. This is the most significant side affect associated with treatment. Peripherally active MOR antagonists can minimize constipation without affecting analgesia. Previously, we described 6β‐Naltrexamine derivative NAP as a novel peripherally selective antagonist. was 300x more potent than methylnaltrexone at improving intestinal motility in morphine...
Abstract Durch Umsetzung entsprechender Dibromide (I) mit dem Hydroxyurethan (II) im Verhältnis l 23 werden die Titelverbindungen (III) dargestellt; Falle der cis‐ bzw. trans‐Verbindungen (IIIb) bleibt Stereochemie entsprechenden meso‐ racemischen Ausgangsverbindungen erhalten.