A5058803816- Adenosine and Purinergic Signaling
- Neuroscience and Neuropharmacology Research
- Synthesis and Characterization of Heterocyclic Compounds
- Pharmacological Receptor Mechanisms and Effects
- Synthesis and Biological Evaluation
- HIV/AIDS drug development and treatment
- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- DNA and Nucleic Acid Chemistry
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Biochemical and Molecular Research
- Fluorine in Organic Chemistry
- Synthesis of heterocyclic compounds
- Chemical Synthesis and Reactions
- Chemical synthesis and alkaloids
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Reactions of Organic Compounds
- Schizophrenia research and treatment
- Coordination Chemistry and Organometallics
- Pharmacological Effects and Toxicity Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Cardiac Ischemia and Reperfusion
- Nicotinic Acetylcholine Receptors Study
- Epilepsy research and treatment
United States Fish and Wildlife Service
2024
Wokingham Hospital
1998-2008
University of Liverpool
1998-2000
Novo Nordisk (Denmark)
1991-1999
Novo Nordisk (United Kingdom)
1992-1995
Novo Holdings (Denmark)
1990
University of Hertfordshire
1982-1985
Abstract: (R)‐N ‐[4,4‐Bis(3‐methyl‐2‐thienyl)but‐3‐en‐l‐yl]nipecotic acid (NO 328) has previously been shown to be a potent anticonvulsant in both mice and rats. Here, we report that NO 328 is inhibitor of γ‐[ 3 H]aminobutyric ([ H]GABA) uptake rat forebrain synaptosomal preparation (IC 50 = 67 n M ) primary cultures neurons astrocytes. Inhibition [ H]GABA by apparently mixed type when preincubated before uptake; the inhibition competitive without preincubation. itself not substrate for GABA...
Myasthenia gravis (MG) is a neuromuscular disease that results in compromised transmission of electrical signals at the junction (NMJ) from motor neurons to skeletal muscle fibers. As result, patients with MG have reduced function and present symptoms severe weakness fatigue. ClC-1 specific chloride (Cl − ) ion channel plays important roles regulating fiber excitability during intense exercise. Here, we show partial inhibition an orally bioavailable small molecule (NMD670) can restore rat...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe synthesis of novel GABA uptake inhibitors. 1. Elucidation the structure-activity studies leading to choice (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (Tiagabine) as an anticonvulsant drug candidateKnud Erik Andersen, Claus Braestrup, Frederik C. Groenwald, Anker S. Joergensen, B. Nielsen, Ursula Sonnewald, Per O. Soerensen, Peter D. Suzdak, and Lars J. KnutsenCite this: Med. Chem. 1993, 36, 12,...
Optimization of a novel series pyridazin-3-one histamine H3 receptor (H3R) antagonists/inverse agonists identified 6-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2H-pyridazin-3-one (8a, CEP-26401; irdabisant) as lead candidate for potential use in the treatment attentional and cognitive disorders. 8a had high affinity both human (Ki = 2.0 nM) rat 7.2 H3Rs with greater than 1000-fold selectivity over hH1R, hH2R, hH4R subtypes against an vitro panel 418 G-protein-coupled receptors, ion...
The synthesis and pharmacological profile of a series neuroprotective adenosine agonists are described. Novel A(1) with potent central nervous system effects diminished influence on the cardiovascular reported compared to selected reference agonists. novel compounds featured derived structurally from two key lead structures: 2-chloro-N-(1-phenoxy-2-propyl)adenosine (NNC 21-0041, 9) 2-chloro-N-(1-piperidinyl)adenosine 90-1515, 4). characterized in terms their vitro profiles, both binding...
(3R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid 1 (tiagabine, Gabitril) is a potent and selective gamma-aminobutyric (GABA) uptake inhibitor with proven anticonvulsant efficacy in humans. This drug, which has unique mechanism of action among marketed agents, been launched for add-on treatment partial seizures or without secondary generalization patients >12 years age. Using this new agent as benchmark, we have designed two series novel GABA inhibitors remarkable...
The selective adenosine A2A receptor agonists 2-[p-(2-carboxethyl)phenylethylaminol-5′-N-ethylcarboxyamidoadenosine (CGS 21680), N-[2-(3,5-dimethoxyphenyl)ethyl]adenosine (DPMA) and metrifudil were investigated for their ability to prevent the loss of pyramidal CA1 neurons in hippocampus following 5 min severe temporary forebrain ischemia mongolian gerbils. CGS 21680, when administered at 18.7 μmol/kg 30 120 reperfusion, exhibited highly significant protection against neuronal loss, but was...
By bioisosteric transformations and successive optimization of known GABA uptake inhibitors, several series novel inhibitors have been prepared by different synthetic approaches. These compounds are derivatives nipecotic acid guvacine, substituted at the nitrogen these amino acids various lipophilic moieties such as diarylaminoalkoxyalkyl or diarylalkoxyalkyl. The in vitro values for inhibition [(3)H]GABA rat synaptosomes was determined each compound, it found that most potent compound from...
Highly pathogenic H5N1 (HP H5N1) influenza A virus (IAV) has been detected annually in North American ducks since its introduction during 2021, but it is unknown if this will follow the same seasonal and geographic patterns that have observed with low-pathogenicity (LP) IAV reservoir. We monitored blue-winged teal Mississippi flyway prior to detection of HP two post-introduction migration cycles from spring 2022 2024, testing birds for infection antibodies nucleoprotein (NP), hemagglutinin...
A short synthesis of imidazo-fused bridgehead-nitrogen 2′-deoxyribo-C-nucleosides has been developed. This is based on a coupling–elimination reaction 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid with series aminoalkyl-substituted heterocycles and alcohols. The intermediate α,β-unsaturated carboxamides esters thus formed are converted into novel imidazo[1,5-a]pyridine, imidazo[1,5-b]pyridazine, imidazo[5,1-f][1,2,4]triazine 2′-deoxyribo-C-nucleosides, including analogues 2′-deoxyguanosine...
Abstract The various synthetic approaches to 2′-deoxyribo-C-nucleosides are summarized. These divided into four groups. Emphasis is placed on the techniques used in determination of anomeric configuration products.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and antiviral properties of 5-(2-substituted vinyl)-6-aza-2'-deoxyuridinesWilliam L. Mitchell, Paul Ravenscroft, Malcolm Hill, Lars J. S. Knutsen, Brian D. Judkins, Roger F. Newton, David I. C. ScopesCite this: Med. Chem. 1986, 29, 5, 809–816Publication Date (Print):May 1, 1986Publication History Published online1 May 2002Published inissue 1 1986https://doi.org/10.1021/jm00155a035RIGHTS & PERMISSIONSArticle...
A short, efficient synthesis of novel imidazo-fused bridgehead-nitrogen C-nucleosides has been developed. Dehydrative coupling 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid (14) with a series aminoalkyl-substituted heterocycles (6)–(8) gives the amides (15)–(17). The latter are subsequently converted into imidazo[1,5-a]pyridine, imidazo[1,5-a]pyrazine, imidazo[1,5-b]pyridazine, and imidazo[5,1-f]-1,2,4-triazine (20) (21). adenosine isostere, 8-amino-3-β-D-ribofuranosylimidazo[1,5-a]pyrazine...