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Your search keyword '"Decicco, C P"' showing total 5 results
Start Over Author "Decicco, C P" Journal bioorganic medicinal chemistry letters
5 results on '"Decicco, C P"'

1. Glutamyl-gamma-boronate inhibitors of bacterial Glu-tRNA(Gln) amidotransferase.

Author

Decicco CP, Nelson DJ, Luo Y, Shen L, Horiuchi KY, Amsler KM, Foster LA, Spitz SM, Merrill JJ, Sizemore CF, Rogers KC, Copeland RA, and Harpel MR

Subjects
Drug Evaluation, Preclinical, Inhibitory Concentration 50, Microbial Sensitivity Tests, Structure-Activity Relationship, Anti-Infective Agents chemistry, Anti-Infective Agents pharmacology, Boronic Acids chemistry, Boronic Acids pharmacology, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Nitrogenous Group Transferases antagonists & inhibitors
Abstract

Analogues of glutamyl-gamma-boronate (1) were synthesized as mechanism-based inhibitors of bacterial Glu-tRNA(Gln) amidotransferase (Glu-AdT) and were designed to engage a putative catalytic serine nucleophile required for the glutaminase activity of the enzyme. Although 1 provides potent enzyme inhibition, structure-activity studies revealed a narrow range of tolerated chemical changes that maintained activity. Nonetheless, growth inhibition of organisms that require Glu-AdT by the most potent enzyme inhibitors appears to validate mechanism-based inhibitor design of Glu-AdT as an approach to antimicrobial development.

Published
2001
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2. Alpha-ketoamides, alpha-ketoesters and alpha-diketones as HCV NS3 protease inhibitors.

Author

Han W, Hu Z, Jiang X, and Decicco CP

Subjects
Amides chemistry, Amino Acid Sequence, Esters chemistry, Hepacivirus drug effects, Hepacivirus metabolism, Ketones chemistry, Serine Proteinase Inhibitors chemistry, Ketones pharmacology, Serine Proteinase Inhibitors pharmacology, Viral Nonstructural Proteins pharmacology
Abstract

Peptide-based alpha-ketoamides, alpha-ketoesters and alpha-diketones were designed, synthesized and evaluated against HCV NS3 protease. Alpha-ketoamides have the highest affinity among the three classes, with 8 being the most potent inhibitor with an IC50 of 340 nM.

Published
2000
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3. P1, P2'-linked macrocyclic amine derivatives as matrix metalloproteinase inhibitors.

Author

Duan JJ, Chen L, Xue CB, Wasserman ZR, Hardman KD, Covington MB, Copeland RR, Arner EC, and Decicco CP

Subjects
Amines chemistry, Computer Simulation, Models, Molecular, Protease Inhibitors chemistry, Amines pharmacology, Extracellular Matrix enzymology, Metalloendopeptidases antagonists & inhibitors, Protease Inhibitors pharmacology
Abstract

A novel series of 13- and 14-membered macrocyclic amines was developed by linking the P1 and P2' groups. The synthesis entails stereoselective Frater alkylation to install the anti-succinate configuration and macrocyclic amination via nucleophilic displacement. This strategy resulted in a new class of conformationally constrained inhibitors that are potent and selective for MMP-8 and 9 over MMP-1 and 3.

Published
1999
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4. Macrocyclic hydroxamate inhibitors of matrix metalloproteinases and TNF-alpha production.

Author

Cherney RJ, Wang L, Meyer DT, Xue CB, Arner EC, Copeland RA, Covington MB, Hardman KD, Wasserman ZR, Jaffee BD, and Decicco CP

Subjects
Crystallography, X-Ray, Humans, Inhibitory Concentration 50, Kinetics, Lipopolysaccharides metabolism, Matrix Metalloproteinase 1, Matrix Metalloproteinase 9, Matrix Metalloproteinase Inhibitors, Metalloendopeptidases classification, Models, Chemical, Models, Molecular, Hydroxamic Acids chemistry, Metalloendopeptidases antagonists & inhibitors, Tumor Necrosis Factor-alpha antagonists & inhibitors
Abstract

Several macrocyclic, hydroxamate derivatives were synthesized and evaluated as inhibitors of matrix metalloproteinases (MMPs) and tumour necrosis factor-alpha (TNF-alpha) production. These macrocycles are anti-succinate based inhibitors linked from P1 to P2'. A variety of functionality was installed at the P1-P2' linkage, which gave inhibitors that displayed excellent MMP inhibition and good TNF-alpha suppression.

Published
1999
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5. Structure-based design and synthesis of a series of hydroxamic acids with a quaternary-hydroxy group in P1 as inhibitors of matrix metalloproteinases.

Author

Jacobson IC, Reddy PG, Wasserman ZR, Hardman KD, Covington MB, Arner EC, Copeland RA, Decicco CP, and Magolda RL

Subjects
Catalytic Domain, Collagenases chemistry, Computer Simulation, Drug Design, Enzyme Precursors antagonists & inhibitors, Enzyme Precursors chemistry, Hydrogen Bonding, Hydroxamic Acids chemical synthesis, Hydroxamic Acids pharmacology, Indicators and Reagents, Matrix Metalloproteinase 1, Matrix Metalloproteinase 3 chemistry, Matrix Metalloproteinase Inhibitors, Metalloendopeptidases chemistry, Models, Molecular, Molecular Conformation, Molecular Structure, Protease Inhibitors chemical synthesis, Protease Inhibitors pharmacology, Protein Conformation, Structure-Activity Relationship, Hydroxamic Acids chemistry, Metalloendopeptidases antagonists & inhibitors, Protease Inhibitors chemistry
Abstract

Examination of the S1 area of the active site of pro-stromelysin has led us to the design of novel and potent inhibitors of matrix metalloproteinases containing constrained quaternary-hydroxy group at P1. The synthesis and biological activity of these compounds with variations at P1', P2', and P3' will be described.

Published
1998
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