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Your search keyword '"Carol F. Petras"' showing total 3 results
Start Over Author "Carol F. Petras" Topic heteroatom
3 results on '"Carol F. Petras"'

1. 5-Heteroatom substituted pyrazoles as canine COX-2 inhibitors. Part III: Molecular modeling studies on binding contribution of 1-(5-methylsulfonyl)pyrid-2-yl and 4-nitrile

Author

Xinjun Hou, Kristin M. Lundy DeMello, Carol F. Petras, Subas M. Sakya, Cheng Hengmiao, Martha L. Minich, Donald W. Mann, Bryson Rast, Burton H. Jaynes, Michelle L. Haven, Scott B. Seibel, Andrei Shavnya, and Jin Li

Subjects
Models, Molecular, Nitrile, Molecular model, Pyridines, Stereochemistry, Clinical Biochemistry, Heteroatom, Pharmaceutical Science, In Vitro Techniques, Pyrazole, Biochemistry, Chemical synthesis, Sulfone, Structure-Activity Relationship, chemistry.chemical_compound, Dogs, Nitriles, Drug Discovery, Animals, Humans, Structure–activity relationship, heterocyclic compounds, Sulfones, Molecular Biology, Sulfonamides, Binding Sites, Cyclooxygenase 2 Inhibitors, Hydrogen bond, organic chemicals, Organic Chemistry, Hydrogen Bonding, Kinetics, chemistry, Celecoxib, Drug Design, Cyclooxygenase 1, Pyrazoles, Molecular Medicine, Indicators and Reagents
Abstract

The structure-activity relationship toward canine COX-1 and COX-2 in vitro whole blood activity of 4-hydrogen versus 4-cyano substituted 5-aryl or 5-heteroatom substituted N-phenyl versus N-2-pyridyl sulfone pyrazoles is discussed. The differences between the pairs of compounds with the 4-nitrile pyrazole derivatives having substantially improved in vitro activity are highlighted for both COX-2 and COX-1. This difference in activity may be due to the contribution of the hydrogen bond of the 4-cyano group with Ser 530 as shown by our molecular modeling studies. In addition, our model suggests a potential contribution from hydrogen bonding of the pyridyl nitrogen to Tyr 355 for the increased activity over the phenyl sulfone analogs.

Published
2007
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2. 5-Heteroatom substituted pyrazoles as canine COX-2 inhibitors. Part 1: Structure–activity relationship studies of 5-alkylamino pyrazoles and discovery of a potent, selective, and orally active analog

Author

Suzanne H. St. Denis, Michelle L. Haven, Scott B. Seibel, Carol F. Petras, Subas M. Sakya, Lisa A. Lund, Annette M. Silvia, Michael P. Lynch, Bryson Rast, Cheng Hengmiao, Martha L. Minich, Burton H. Jaynes, Kristin M. Lundy DeMello, Donald W. Mann, Andrei Shavnya, Anne Hickman, Ziegler Carl B, David A. Koss, David M. George, Robert J. Rafka, and Jin Li

Subjects
Stereochemistry, Clinical Biochemistry, Heteroatom, Drug Evaluation, Preclinical, Administration, Oral, Pharmaceutical Science, In Vitro Techniques, Biochemistry, Chemical synthesis, Sulfone, Structure-Activity Relationship, chemistry.chemical_compound, Dogs, In vivo, Drug Discovery, Animals, Structure–activity relationship, Molecular Biology, chemistry.chemical_classification, Cyclooxygenase 2 Inhibitors, Molecular Structure, biology, Organic Chemistry, In vitro, Disease Models, Animal, Enzyme, chemistry, Cyclooxygenase 2, Enzyme inhibitor, Cats, biology.protein, Pyrazoles, Molecular Medicine
Abstract

Structure-activity relationship (SAR) studies of the novel 2-[3-di and trifluoromethyl-5-alkylamino pyrazo-1-yl]-5-methanesulfonyl (SO(2)Me)/sulfamoyl (SO(2)NH(2))-pyridine derivatives for canine COX enzymes are described. The studies led to the identification of 2e as lead with potent in vitro activity, selectivity, and in vivo activity in dogs and cats.

Published
2006
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3. 5-Heteroatom-substituted pyrazoles as canine COX-2 inhibitors: Part 2. Structure-activity relationship studies of 5-alkylethers and 5-thioethers

Author

David A. Koss, Cheng Hengmiao, Martha L. Minich, Robert J. Rafka, Ziegler Carl B, Anne Hickman, Jason K. Dutra, Annette M. Silvia, Jin Li, Michael P. Lynch, Chao Li, Andrei Shavnya, Michelle L. Haven, Scott B. Seibel, Bryson Rast, David M. George, Kristin M. Lundy DeMello, Donald W. Mann, Burton H. Jaynes, Carol F. Petras, and Subas M. Sakya

Subjects
Alkylation, Stereochemistry, Clinical Biochemistry, Heteroatom, Pharmaceutical Science, Thio, Ether, Biochemistry, Chemical synthesis, Sulfone, chemistry.chemical_compound, Inhibitory Concentration 50, Structure-Activity Relationship, Dogs, Drug Discovery, Structure–activity relationship, Animals, Sulfhydryl Compounds, Molecular Biology, biology, Cyclooxygenase 2 Inhibitors, Molecular Structure, Chemistry, Organic Chemistry, Enzyme inhibitor, Cyclooxygenase 2, biology.protein, Molecular Medicine, Pyrazoles, Ethers
Abstract

Structure-activity relationship (SAR) studies of novel 2-[3-trifluoromethyl-5-alkyl(thio)ether pyrazo-1-yl]-5-methanesulfonyl pyridine derivatives for canine COX enzymes are described. The 4-cyano-5-alkyl ethers were found to have excellent potency and selectivity, whereas the 5-thioethers were potent but less selective than the ether analogs in a canine whole blood (CWB) COX-2 assay.

Published
2005

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