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Your search keyword '"Larry K. Keefer"' showing total 8 results
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8 results on '"Larry K. Keefer"'

1. Nitric Oxide Prodrugs: Diazeniumdiolate Anions of Hindered Secondary Amines

Author

Harinath Chakrapani, Michael L. Citro, Brett M. Showalter, Larry K. Keefer, and Joseph E. Saavedra

Subjects
Molecular Structure, Extramural, Organic Chemistry, chemistry.chemical_element, Prodrug, Nitric Oxide, Biochemistry, Decomposition, Nitrogen, Combinatorial chemistry, Nitric oxide, chemistry.chemical_compound, chemistry, Aqueous buffer, Organic chemistry, Prodrugs, Amines, Physical and Theoretical Chemistry, Azo Compounds
Abstract

Nitric oxide prodrugs derived from hindered secondary amines were prepared. The decomposition patterns of these prodrugs indicate that alpha-methyl groups around the nitrogen bearing the diazeniumdiolate group prolong their half-life in aqueous buffer.

Published
2007
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2. A Nitric Oxide-Releasing Polydiazeniumdiolate Derived from Acetonitrile

Author

Ernst V. Arnold, Joseph A. Hrabie, and Larry K. Keefer, and Michael L. Citro

Subjects
Acetonitriles, Magnetic Resonance Spectroscopy, Aqueous solution, Spectrophotometry, Infrared, Organic Chemistry, Kinetics, Inorganic chemistry, Nitrous oxide, Reference Standards, Nitric Oxide, Biochemistry, Medicinal chemistry, Nitric oxide, Solvent, chemistry.chemical_compound, Hydrolysis, chemistry, Nucleophile, Solvents, Indicators and Reagents, Spectrophotometry, Ultraviolet, Physical and Theoretical Chemistry, Acetonitrile, Azo Compounds
Abstract

Acetonitrile, frequently used as a solvent in reactions of nitric oxide (NO) with amines and other nucleophiles to introduce the [N(O)NO](-) (diazeniumdiolate) functional group, has itself been shown to react with NO in the presence of strong base to yield methane trisdiazeniumdiolate (1), presumably via an intermediate trisdiazeniumdiolated imidate. Aqueous hydrolysis of 1 does not follow simple first-order kinetics and produces mixtures of NO and nitrous oxide in ratios that vary with solution pH. [reaction: see text]

Published
2002
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3. Glycosylated PROLI/NO derivatives as nitric oxide prodrugs

Author

Michael L. Citro, Rahul S. Nandurdikar, Harinath Chakrapani, Sam Y. Hong, Anna E. Maciag, Joseph E. Saavedra, and Larry K. Keefer

Subjects
chemistry.chemical_classification, Glycosylation, Molecular Structure, Proline, Organic Chemistry, Peptide, Prodrug, Nitric Oxide, Biochemistry, Combinatorial chemistry, Article, Nitric oxide, chemistry.chemical_compound, Residue (chemistry), chemistry, Acetylglucosaminidase, Organic chemistry, Prodrugs, Physical and Theoretical Chemistry, Intracellular
Abstract

GlcNAc-PROLI/NO prodrugs that are activated by N-acetylglucosaminidase to release nitric oxide (NO) are described. A classical acid−amine coupling is used to bifunctionalize these PROLI/NO prodrugs, which on activation generate up to 4 mol of NO, a peptide residue, and an N-acetylglucosamine residue. Many of the prodrugs synthesized are efficient sources of intracellular NO.

Published
2009

4. Cell-permeable esters of diazeniumdiolate-based nitric oxide prodrugs

Author

Larry K. Keefer, Joseph E. Saavedra, Harinath Chakrapani, Michael L. Citro, and Anna E. Maciag

Subjects
Human leukemia, Carboxylic acid, Cell, Intracellular Space, Nitric Oxide, Biochemistry, Permeability, Article, Nitric oxide, chemistry.chemical_compound, Cell Line, Tumor, medicine, Animals, Humans, Prodrugs, Physical and Theoretical Chemistry, Cell Proliferation, chemistry.chemical_classification, Cell growth, Organic Chemistry, Glutathione, Prodrug, Rats, medicine.anatomical_structure, chemistry, Azo Compounds, Intracellular
Abstract

[Image: see text] Although O(2)-(2,4-dinitrophenyl) derivatives of diazeniumdiolate-based nitric oxide (NO) prodrugs bearing a free carboxylic acid group were activated by glutathione to release NO, these compounds were poor sources of intracellular NO and showed diminished anti-proliferative activity against human leukemia HL-60 cells. The carboxylic acid esters of these prodrugs, however, were found to be superior sources of intracellular NO and potent inhibitors of HL-60 cell proliferation.

Published
2008

5. V-PROLI/NO, a prodrug of the nitric oxide donor, PROLI/NO

Author

Joseph E. Saavedra, Brett M. Showalter, Larry K. Keefer, Li Kong, and Harinath Chakrapani

Subjects
Vinyl Compounds, Proline, Stereochemistry, Chemistry, Organic Chemistry, Metabolism, Prodrug, Biochemistry, Nitric oxide, V-PROLI-NO, chemistry.chemical_compound, Electrophilic substitution, Cytochrome P-450 Enzyme System, Microsome, Microsomes, Liver, Organic chemistry, Humans, Protein Isoforms, Hydroxymethyl, Nitric Oxide Donors, Prodrugs, Physical and Theoretical Chemistry, Liver microsomes
Abstract

The sensitivity to decomposition of the nitric oxide (NO) donor ion, 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), complicates direct electrophilic substitution to form useful prodrug derivatives. A modified general synthetic approach involving 1-[2-(hydroxymethyl)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate ion (structure A, above) was used to prepare several PROLI/NO prodrugs including the previously inaccessible O2-vinyl derivative, V-PROLI/NO. Metabolism of V-PROLI/NO by liver microsomes enriched in human cytochrome P450 isoforms was demonstrated.

Published
2007

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