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Your search keyword '"Decicco, C P"' showing total 8 results
Start Over Author "Decicco, C P" Topic protease inhibitors
8 results on '"Decicco, C P"'

1. Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)- [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent, selective, and orally bioavailable aggrecanase inhibitors.

Author

Yao W, Wasserman ZR, Chao M, Reddy G, Shi E, Liu RQ, Covington MB, Arner EC, Pratta MA, Tortorella M, Magolda RL, Newton R, Qian M, Ribadeneira MD, Christ D, Wexler RR, and Decicco CP

Subjects
Administration, Oral, Animals, Asparagine analogs & derivatives, Asparagine chemistry, Asparagine pharmacokinetics, Asparagine pharmacology, Biological Availability, Dogs, Drug Design, Endopeptidases chemistry, Hydroxamic Acids chemistry, Hydroxamic Acids pharmacokinetics, Hydroxamic Acids pharmacology, Matrix Metalloproteinase 1 chemistry, Matrix Metalloproteinase 2 chemistry, Matrix Metalloproteinase 8 chemistry, Matrix Metalloproteinase 9 chemistry, Models, Molecular, Protease Inhibitors chemistry, Protease Inhibitors pharmacokinetics, Protease Inhibitors pharmacology, Protein Binding, Stereoisomerism, Structure-Activity Relationship, Asparagine chemical synthesis, Endopeptidases metabolism, Hydroxamic Acids chemical synthesis, Protease Inhibitors chemical synthesis
Abstract

A pharmacophore model of the P1' site, specific for aggrecanase, was defined using the specificity studies of the matrix metalloproteinases and the similar biological activity of aggrecanase and MMP-8. Incorporation of the side chain of a tyrosine residue into compound 1 as the P1' group provided modest selectivity for aggrecanase over MMP-1, -2, and -9. A cis-(1S)(2R)-amino-2-indanol scaffold was incorporated as a tyrosine mimic (P2') to conformationally constrain 2. Further optimization resulted in compound 11, a potent, selective, and orally bioavailable inhibitor of aggrecanase.

Published
2001
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2. Discovery of macrocyclic hydroxamic acids containing biphenylmethyl derivatives at P1', a series of selective TNF-alpha converting enzyme inhibitors with potent cellular activity in the inhibition of TNF-alpha release.

Author

Xue CB, He X, Corbett RL, Roderick J, Wasserman ZR, Liu RQ, Jaffee BD, Covington MB, Qian M, Trzaskos JM, Newton RC, Magolda RL, Wexler RR, and Decicco CP

Subjects
ADAM Proteins, ADAM17 Protein, Binding Sites, Heterocyclic Compounds, 1-Ring chemistry, Heterocyclic Compounds, 1-Ring pharmacology, Humans, Hydroxamic Acids chemistry, Hydroxamic Acids pharmacology, Lipopolysaccharides pharmacology, Models, Molecular, Protease Inhibitors chemistry, Protease Inhibitors pharmacology, Protein Binding, Structure-Activity Relationship, Tumor Necrosis Factor-alpha metabolism, Heterocyclic Compounds, 1-Ring chemical synthesis, Hydroxamic Acids chemical synthesis, Metalloendopeptidases antagonists & inhibitors, Protease Inhibitors chemical synthesis, Tumor Necrosis Factor-alpha antagonists & inhibitors
Abstract

SAR exploration at P1' using an anti-succinate-based macrocyclic hydroxamic acid as a template led to the identification of several bulky biphenylmethyl P1' derivatives which confer potent porcine TACE and anti-TNF-alpha cellular activities with high selectivity versus most of the MMPs screened. Our studies demonstrate for the first time that TACE has a larger S1' pocket in comparison to MMPs and that potent and selective TACE inhibitors can be achieved by incorporation of sterically bulky P1' residues.

Published
2001
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3. Intramolecular O-arylation of phenols with phenylboronic acids: application to the synthesis of macrocyclic metalloproteinase inhibitors.

Author

Decicco CP, Song Y, and Evans DA

Subjects
Collagenases, Copper chemistry, Cyclization, Drug Design, Humans, Molecular Structure, Protease Inhibitors chemistry, Boronic Acids chemistry, Matrix Metalloproteinase Inhibitors, Phenols chemistry, Protease Inhibitors chemical synthesis
Abstract

[reaction: see text]. The copper acetate mediated intramolecular O-arylation of phenols with phenylboronic acid pseudopeptides is the key step in the preparation of macrocyclic biphenyl ether hydroxamic acid inhibitors of collagenase 1 and gelatinases A and B. The intramolecular macrocyclization was found to be mild and tolerant of common chemical functionality. This methodology should provide a general route to macrocyclic biphenyl ethers.

Published
2001
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4. 1-Aminocyclopropaneboronic acid: synthesis and incorporation into an inhibitor of hepatitis C virus NS3 protease.

Author

Priestley ES and Decicco CP

Subjects
Boronic Acids chemistry, Cyclopropanes chemistry, Boronic Acids chemical synthesis, Cyclopropanes chemical synthesis, Hepatitis C enzymology, Oligopeptides chemistry, Protease Inhibitors chemical synthesis, Viral Nonstructural Proteins antagonists & inhibitors
Abstract

The previously unreported alpha,alpha-disubstituted 1-aminoboronate esters have potential utility in peptidomimetic design, particularly against serine protease targets. A concise synthesis of 1-aminocyclopropaneboronate pinanediol ester is reported, and a peptidyl derivative is shown to have modest affinity (K(i) = 1.6 microM) for hepatitis C NS3 protease.

Published
2000
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5. 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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6. Design and synthesis of cyclic inhibitors of matrix metalloproteinases and TNF-alpha production.

Author

Xue CB, He X, Roderick J, DeGrado WF, Cherney RJ, Hardman KD, Nelson DJ, Copeland RA, Jaffee BD, and Decicco CP

Subjects
Crystallography, X-Ray, Humans, Hydroxamic Acids blood, Hydroxamic Acids chemistry, Hydroxamic Acids pharmacology, In Vitro Techniques, Lactams blood, Lactams chemistry, Lactams pharmacology, Lipopolysaccharides blood, Lipopolysaccharides pharmacology, Lymphocyte Activation, Matrix Metalloproteinase 1, Matrix Metalloproteinase 9, Matrix Metalloproteinase Inhibitors, Metalloendopeptidases blood, Models, Molecular, Protease Inhibitors chemistry, Protease Inhibitors pharmacology, Hydroxamic Acids chemical synthesis, Lactams chemical synthesis, Metalloendopeptidases antagonists & inhibitors, Protease Inhibitors chemical synthesis, Tumor Necrosis Factor-alpha antagonists & inhibitors
Published
1998
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7. Macrocyclic amino carboxylates as selective MMP-8 inhibitors.

Author

Cherney RJ, Wang L, Meyer DT, Xue CB, Wasserman ZR, Hardman KD, Welch PK, Covington MB, Copeland RA, Arner EC, DeGrado WF, and Decicco CP

Subjects
Matrix Metalloproteinase 8, Models, Molecular, Molecular Structure, Structure-Activity Relationship, Drug Design, Lactams chemical synthesis, Lactams chemistry, Lactams pharmacology, Matrix Metalloproteinase Inhibitors, Protease Inhibitors chemical synthesis, Protease Inhibitors chemistry, Protease Inhibitors pharmacology
Published
1998
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8. 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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