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Your search keyword '"Thomas M. Connolly"' showing total 4 results
Start Over Author "Thomas M. Connolly" Journal bioorganicmedicinal chemistry letters
4 results on '"Thomas M. Connolly"'

1. Cyclic benzamidines as orally efficacious NR2B-selective NMDA receptor antagonists

Author

Rodney A. Bednar, Cindra L. Condra, Brian E. Libby, Bohumil Bednar, Kenneth S. Koblan, Nigel J. Liverton, Stanley L. Gaul, Scott D. Mosser, Joseph J. Lynch, Gary L. Stump, David A. Claremon, Kevin Nguyen, Thomas M. Connolly, Christopher F. Claiborne, and John A. McCauley

Subjects
Stereochemistry, Clinical Biochemistry, Analgesic, Pharmaceutical Science, Administration, Oral, Pain, Pharmacology, Biochemistry, Models, Biological, Receptors, N-Methyl-D-Aspartate, Oral administration, Drug Discovery, medicine, Animals, Molecular Biology, Chemistry, Organic Chemistry, Glutamate receptor, Antagonist, Benzamidines, Rats, nervous system, Hyperalgesia, Excitatory Amino Acid Antagonists, Molecular Medicine, NMDA receptor, medicine.symptom
Abstract

A novel series of cyclic benzamidines was synthesized and shown to exhibit NR2B-subtype selective NMDA antagonist activity. Compound 29 is orally active in a carrageenan-induced rat hyperalgesia model of pain.

Published
2007

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. Discovery of a nonpeptidic small molecule antagonist of the human platelet thrombin receptor (PAR-1)

Author

Kenneth E. Rittle, Mary Beth Young, Roger M. Freidinger, G. F. Lundell, Stanley L. Gaul, Philippe G. Nantermet, James C. Barrow, Robert J. Gould, Cindra L. Condra, Kris Prendergast, Janetta M. Pellicore, Harold G. Selnick, Rodney A. Bednar, Jerzy Karczewski, and Thomas M. Connolly

Subjects
Agonist, Blood Platelets, Platelet Aggregation, medicine.drug_class, Clinical Biochemistry, Pharmaceutical Science, Pharmacology, In Vitro Techniques, Biochemistry, Chemical synthesis, Structure-Activity Relationship, Thrombin, Piperidines, Drug Discovery, Thrombin receptor, medicine, Humans, Receptor, PAR-1, Platelet activation, Molecular Biology, Chemistry, Organic Chemistry, Antagonist, Azepines, Isoxazoles, Platelet Activation, Small molecule, In vitro, Peptide Fragments, Drug Design, Molecular Medicine, Indicators and Reagents, Receptors, Thrombin, Platelet Aggregation Inhibitors, medicine.drug
Abstract

The synthesis and biological evaluation of a series of nonpeptidic small molecule antagonists of the human platelet thrombin receptor (PAR-1) are described. Optimization of the 5-amino-3-arylisoxazole lead resulted in an approximate 100-fold increase in potency. The most potent of these compounds (54) inhibits platelet activation with IC50s of 90 nM against the thrombin receptor agonist peptide (TRAP) and 510 nM against thrombin as the agonist. Further, antagonist 54 fully blocks platelet aggregation stimulated by 1 nM thrombin for 10 min.

Published
2002

4. Discovery and initial structure-activity relationships of trisubstituted ureas as thrombin receptor (PAR-1) antagonists

Author

Andrew M. Stern, Phung L. Ngo, James C. Barrow, Thomas M. Connolly, Janetta M. Pellicore, Michael J. Breslin, Mary Beth Young, Roger M. Freidinger, Harold G. Selnick, Jerzy Karczewski, Cindra L. Condra, John H. Hutchinson, Stanley L. Gaul, Philippe G. Nantermet, Robert J. Gould, Kristen L. Glass, and Rodney A. Bednar

Subjects
Agonist, medicine.drug_class, Clinical Biochemistry, Pharmaceutical Science, Biochemistry, Structure-Activity Relationship, Thrombin, Drug Discovery, Thrombin receptor, medicine, Urea, Protease-activated receptor, Platelet, Receptor, PAR-1, Platelet activation, Receptor, Molecular Biology, Protease-activated receptor 2, Chemistry, Organic Chemistry, Platelet Activation, Molecular Medicine, Receptors, Thrombin, circulatory and respiratory physiology, medicine.drug
Abstract

Thrombin is the most potent agonist of platelet activation, and its effects are predominantly mediated by platelet thrombin receptors. Therefore, antagonists of the thrombin receptor have potential utility for the treatment of thrombotic disorders. Screening of combinatorial libraries revealed 2 to be a potent antagonist of the thrombin receptor. Modifications of this structure produced 11k, which inhibits thrombin receptor stimulated secretion and aggregation of platelets.

Published
2001

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