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Your search keyword '"Popovici-Muller J"' showing total 5 results
Start Over Author "Popovici-Muller J" Topic adam proteins
5 results on '"Popovici-Muller J"'

1. 2-(2-Aminothiazol-4-yl)pyrrolidine-based tartrate diamides as potent, selective and orally bioavailable TACE inhibitors.

Author

Dai C, Li D, Popovici-Muller J, Zhao L, Girijavallabhan VM, Rosner KE, Lavey BJ, Rizvi R, Shankar BB, Wong MK, Guo Z, Orth P, Strickland CO, Sun J, Niu X, Chen S, Kozlowski JA, Lundell DJ, Piwinski JJ, Shih NY, and Siddiqui MA

Subjects
ADAM17 Protein, Amides chemical synthesis, Amides chemistry, Animals, Biological Availability, Enzyme Activation drug effects, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Molecular Structure, Rats, ADAM Proteins antagonists & inhibitors, Amides pharmacology, Enzyme Inhibitors pharmacology, Pyrrolidines chemistry, Tartrates chemistry
Abstract

TNF-α converting enzyme (TACE) inhibitors are promising agents to treat inflammatory disorders and cancer. We have investigated novel tartrate diamide TACE inhibitors where the tartrate core binds to zinc in a unique tridentate fashion. Incorporating (R)-2-(2-N-alkylaminothiazol-4-yl)pyrrolidines into the left hand side amide of the tartrate scaffold led to the discovery of potent and selective TACE inhibitors, some of which exhibited good rat oral bioavailability., (Copyright © 2011. Published by Elsevier Ltd.)

Published
2011
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2. Novel TNF-α converting enzyme (TACE) inhibitors as potential treatment for inflammatory diseases.

Author

Girijavallabhan VM, Chen L, Dai C, Feltz RJ, Firmansjah L, Li D, Kim SH, Kozlowski JA, Lavey BJ, Kosinski A, Piwinski JJ, Popovici-Muller J, Rizvi R, Rosner KE, Shankar BB, Shih NY, Siddiqui MA, Tong L, Wong MK, Yang DY, Yang L, Yu W, Zhou G, Guo Z, Orth P, Madison V, Bian H, Lundell D, Niu X, Shah H, Sun J, and Umland S

Subjects
ADAM Proteins metabolism, ADAM17 Protein, Acetylene analogs & derivatives, Acetylene pharmacokinetics, Acetylene therapeutic use, Animals, Anti-Inflammatory Agents pharmacokinetics, Anti-Inflammatory Agents therapeutic use, Dogs, Haplorhini, Humans, Protease Inhibitors pharmacokinetics, Protease Inhibitors therapeutic use, Rats, ADAM Proteins antagonists & inhibitors, Anti-Inflammatory Agents chemistry, Arthritis, Rheumatoid drug therapy, Protease Inhibitors chemistry
Abstract

Our research on hydantoin based TNF-α converting enzyme (TACE) inhibitors has led to an acetylene containing series that demonstrates sub-nanomolar potency (K(i)) as well as excellent activity in human whole blood. These studies led to the discovery of highly potent TACE inhibitors with good DMPK profiles., (Published by Elsevier Ltd.)

Published
2010
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3. Structure and activity relationships of tartrate-based TACE inhibitors.

Author

Li D, Popovici-Muller J, Belanger DB, Caldwell J, Dai C, David M, Girijavallabhan VM, Lavey BJ, Lee JF, Liu Z, Mazzola R, Rizvi R, Rosner KE, Shankar B, Spitler J, Ting PC, Vaccaro H, Yu W, Zhou G, Zhu Z, Niu X, Sun J, Guo Z, Orth P, Chen S, Kozlowski JA, Lundell DJ, Madison V, McKittrick B, Piwinski JJ, Shih NY, Shipps GW Jr, Siddiqui MA, and Strickland CO

Subjects
ADAM Proteins metabolism, ADAM17 Protein, Animals, Binding Sites, Computer Simulation, Protease Inhibitors chemical synthesis, Protease Inhibitors pharmacokinetics, Rats, Structure-Activity Relationship, Tartrates chemical synthesis, Tartrates pharmacokinetics, ADAM Proteins antagonists & inhibitors, Protease Inhibitors chemistry, Tartrates chemistry
Abstract

The syntheses and structure-activity relationships of the tartrate-based TACE inhibitors are discussed. The optimization of both the prime and non-prime sites led to compounds with picomolar activity. Several analogs demonstrated good rat pharmacokinetics., (2010 Elsevier Ltd. All rights reserved.)

Published
2010
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4. Discovery and SAR of hydantoin TACE inhibitors.

Author

Yu W, Guo Z, Orth P, Madison V, Chen L, Dai C, Feltz RJ, Girijavallabhan VM, Kim SH, Kozlowski JA, Lavey BJ, Li D, Lundell D, Niu X, Piwinski JJ, Popovici-Muller J, Rizvi R, Rosner KE, Shankar BB, Shih NY, Siddiqui MA, Sun J, Tong L, Umland S, Wong MK, Yang DY, and Zhou G

Subjects
ADAM17 Protein, Enzyme Inhibitors chemistry, Hydantoins chemistry, Hydrogen Bonding, Models, Molecular, Structure-Activity Relationship, X-Ray Diffraction, ADAM Proteins antagonists & inhibitors, Drug Discovery, Enzyme Inhibitors pharmacology, Hydantoins pharmacology
Abstract

We disclose inhibitors of TNF-alpha converting enzyme (TACE) designed around a hydantoin zinc binding moiety. Crystal structures of inhibitors bound to TACE revealed monodentate coordination of the hydantoin to the zinc. SAR, X-ray, and modeling designs are described. To our knowledge, these are the first reported X-ray structures of TACE with a hydantoin zinc ligand., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Published
2010
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5. The discovery of novel tartrate-based TNF-alpha converting enzyme (TACE) inhibitors.

Author

Rosner KE, Guo Z, Orth P, Shipps GW Jr, Belanger DB, Chan TY, Curran PJ, Dai C, Deng Y, Girijavallabhan VM, Hong L, Lavey BJ, Lee JF, Li D, Liu Z, Popovici-Muller J, Ting PC, Vaccaro H, Wang L, Wang T, Yu W, Zhou G, Niu X, Sun J, Kozlowski JA, Lundell DJ, Madison V, McKittrick B, Piwinski JJ, Shih NY, Arshad Siddiqui M, and Strickland CO

Subjects
ADAM17 Protein, Binding Sites, Combinatorial Chemistry Techniques, Crystallography, X-Ray, Humans, Protease Inhibitors metabolism, Protease Inhibitors pharmacology, Tartrates metabolism, Tartrates pharmacology, ADAM Proteins antagonists & inhibitors, ADAM Proteins metabolism, Drug Discovery methods, Protease Inhibitors chemistry, Tartrates chemistry, Tumor Necrosis Factor-alpha metabolism
Abstract

A novel series of TNF-alpha convertase (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds are bis-amides of L-tartaric acid (tartrate) and coordinate to the active site zinc in a tridentate manner. They are selective for TACE over other MMP's. We report the first X-ray crystal structure for a tartrate-based TACE inhibitor., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Published
2010
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