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Your search keyword '"John W. Butcher"' showing total 3 results
Start Over Author "John W. Butcher" Journal bioorganicmedicinal chemistry letters
3 results on '"John W. Butcher"'

1. Synthesis and evaluation of novel tricyclic benzo[4.5]cyclohepta[1.2]pyridine derivatives as NMDA/NR2B antagonists

Author

Charles J. Mcintyre, Scott D. Mosser, Ken S. Koblan, Michael E. Cunningham, John A. McCauley, Roger M. Freidinger, David A. Claremon, Carl F. Homnick, Nigel J. Liverton, Rodney A. Bednar, John W. Butcher, Stanley L. Gaul, Joseph J. Romano, and Bohumil Bednar

Subjects
Nitrile, Stereochemistry, Pyridines, Clinical Biochemistry, hERG, Pharmaceutical Science, Biochemistry, Chemical synthesis, Receptors, N-Methyl-D-Aspartate, Cell Line, chemistry.chemical_compound, Structure-Activity Relationship, Drug Discovery, Pyridine, Structure–activity relationship, Humans, Molecular Biology, chemistry.chemical_classification, Neurotransmitter Agents, biology, musculoskeletal, neural, and ocular physiology, Organic Chemistry, Ether-A-Go-Go Potassium Channels, Benzocycloheptenes, nervous system, chemistry, biology.protein, Molecular Medicine, NMDA receptor, Selectivity, psychological phenomena and processes, Tricyclic
Abstract

A novel series of annulated tricyclic compounds was synthesized and evaluated as NMDA/NR2B antagonists. Structure-activity development was directed towards in vitro optimization of NR2B activity and selectivity over the hERG K(+) channel. Preferred compounds were subsequently evaluated for selectivity in an alpha(1)-adrenergic receptor binding counter-screen and a cell-based assay of NR2B activity.

Published
2009

2. Synthesis of the first sulfur-35-labeled hERG radioligand

Author

Conrad E. Raab, Steven J. Staskiewicz, David G. Melillo, Dennis C. Dean, Thomas M. Connolly, Jerzy Karczewski, John W. Butcher, Nathan X. Yu, and Nigel J. Liverton

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Stereochemistry, Clinical Biochemistry, hERG, Pharmaceutical Science, Isotopes of sulfur, Sulfur Radioisotopes, Biochemistry, Chemical synthesis, chemistry.chemical_compound, Radioligand Assay, Aniline, Piperidines, Drug Discovery, Radioligand, Potassium Channel Blockers, Humans, Benzopyrans, cardiovascular diseases, Molecular Biology, biology, Organic Chemistry, Diastereomer, General Medicine, Ligand (biochemistry), Combinatorial chemistry, Ether-A-Go-Go Potassium Channels, High specific activity, chemistry, biology.protein, Molecular Medicine, Radiopharmaceuticals
Abstract

The synthesis of the first high specific activity S-35-labeled hERG radioligand, [(35)S]MK-0499, for use in HTS assays of drug candidates for hERG interaction is described. The radioligand is prepared by [(35)S]sulfonylation of a high diastereomeric excess (de) aniline precursor prepared from unlabeled MK-0499.

Published
2005

3. Novel 5-cyclopropyl-1,4-benzodiazepin-2-ones as potent and selective I(Ks)-blocking class III antiarrhythmic agents

Author

Roger M. Freidinger, Kamlesh P. Vyas, John W. Butcher, Joseph J. Lynch, Nancy K. Jurkiewicz, Christine M Dieckhaus, David A. Claremon, Nigel J. Liverton, Jixin Wang, Donald E. Slaughter, and Joseph J. Salata

Subjects
Patch-Clamp Techniques, Potassium Channels, Refractory Period, Electrophysiological, medicine.drug_class, Stereochemistry, medicine.medical_treatment, Clinical Biochemistry, Guinea Pigs, Pharmaceutical Science, Carboxamide, Antiarrhythmic agent, In Vitro Techniques, Biochemistry, Chemical synthesis, Benzodiazepines, Structure-Activity Relationship, Dogs, Heart Rate, Drug Discovery, medicine, Potassium Channel Blockers, Structure–activity relationship, Animals, Humans, Channel blocker, Molecular Biology, Dose-Response Relationship, Drug, Chemistry, Organic Chemistry, Hemodynamics, Potassium channel blocker, Potassium channel, Potassium Channels, Voltage-Gated, Microsomes, Liver, Molecular Medicine, Anti-Arrhythmia Agents, medicine.drug, Delayed Rectifier Potassium Channels
Abstract

Novel 5-cyclopropyl-1,4-benzodiazepin-2-ones having various N-l substituents were identified as potent and selective blockers of the slowly activating cardiac delayed rectifier potassium current (I(Ks)). Compound 11 is the most potent I(Ks) channel blocker reported to date.

Published
2003

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