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Your search keyword '"Marian T. Namovic"' showing total 3 results
Start Over Author "Marian T. Namovic" Journal bioorganicmedicinal chemistry letters
3 results on '"Marian T. Namovic"'

1. Synthesis and activity of N-cyanoguanidine-piperazine P2X7 antagonists

Author

Nathan S. Josephsohn, John W. Maull, Moore Nigel St John, Brian Bettencourt, Morytko Michael J, Lu Wang, Edit Tarcsa, Jonathan George, Biqin Li, Paul Rafferty, Diana L. Donnelly-Roberts, Marian T. Namovic, Patrick Betschmann, Michael Friedman, Jose-Andres Salmeron-Garcia, Gavin C. Hirst, Donald Konopacki, and Woller Kevin R

Subjects
Chemistry, Pharmaceutical, Clinical Biochemistry, Interleukin-1beta, Pharmaceutical Science, Pharmacology, Biochemistry, Chemical synthesis, Guanidines, Piperazines, chemistry.chemical_compound, Inhibitory Concentration 50, Structure-Activity Relationship, In vivo, Drug Discovery, Purinergic P2 Receptor Antagonists, Structure–activity relationship, Animals, Humans, Receptor, Molecular Biology, Piperazine, Whole blood, Molecular Structure, Chemistry, Receptors, Purinergic P2, Organic Chemistry, Biological activity, In vitro, Rats, Models, Chemical, Drug Design, Molecular Medicine, Receptors, Purinergic P2X7
Abstract

A novel series of cyanoguanidine-piperazine P2X(7) antagonists were identified and structure-activity relationship (SAR) studies described. Compounds were assayed for activity at human and rat P2X(7) receptors in addition to their ability to inhibit IL-1 beta release from stimulated human whole blood cultures. Compound 27 possesses potent activity (0.12 microM) in this latter assay and demonstrates moderate clearance in-vivo.

Published
2008

2. Synthesis and in vitro activity of N'-cyano-4-(2-phenylacetyl)-N-o-tolylpiperazine-1-carboximidamide P2X7 antagonists

Author

Haipeng Chen, Morytko Michael J, Anna M. Ericsson, Patrick Betschmann, Diana L. Donnelly-Roberts, Michael F. Jarvis, Marian T. Namovic, William A. Carroll, Paul Rafferty, and Woller Kevin R

Subjects
Nitrile, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, In Vitro Techniques, Biochemistry, Chemical synthesis, Piperazines, chemistry.chemical_compound, Structure-Activity Relationship, Drug Discovery, Purinergic P2 Receptor Antagonists, Structure–activity relationship, Moiety, Animals, Humans, Receptor, Molecular Biology, Molecular Structure, Chemistry, Receptors, Purinergic P2, Organic Chemistry, Antagonist, In vitro, Recombinant Proteins, Rats, Piperazine, Molecular Medicine, Receptors, Purinergic P2X7
Abstract

A novel series of cyanoguanidine-piperazine P2X(7) antagonists was designed based upon the structure of A-740003. Structure-activity relationship (SAR) studies focused on the piperazine moiety and the right hand side substitution. Compounds were assayed for activity at human and rat P2X(7) receptors and compound 29 was found to possess potent activity (IC(50)=30-60 nM) at both species.

Published
2007

3. Novel and potent 3-(2,3-dichlorophenyl)-4-(benzyl)-4H-1,2,4-triazole P2X7 antagonists

Author

Diana L. Donnelly-Roberts, Arturo Perez-Medrano, Alan S. Florjancic, Michael F. Jarvis, Marian T. Namovic, Douglas M. Kalvin, William A. Carroll, George K. Grayson, Prisca Honore, and Ying Wang

Subjects
Isostere, Stereochemistry, Clinical Biochemistry, Triazole, Pharmaceutical Science, Biochemistry, Chemical synthesis, chemistry.chemical_compound, Structure-Activity Relationship, Drug Discovery, Purinergic P2 Receptor Antagonists, Structure–activity relationship, Potency, Animals, Tetrazole, Molecular Biology, Organic Chemistry, 1,2,4-Triazole, General Medicine, Triazoles, Combinatorial chemistry, Rats, chemistry, Triazole derivatives, Molecular Medicine, Receptors, Purinergic P2X7, Lead compound
Abstract

Structure-activity relationship (SAR) studies were conducted around early tetrazole-based leads 3 and 4. Replacements for the tetrazole core were investigated and the pendant benzyl substitution was reoptimized with a triazole isostere. Triazole-based P2X(7) antagonists were identified with similar potency to the lead compound 4 but with improved physiochemical properties. Compound 12 was active in a rat model of neuropathic pain.

Published
2007

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