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Your search keyword '"Gijsen H"' showing total 2 results
Start Over Author "Gijsen H" Journal bioorganic medicinal chemistry letters
2 results on '"Gijsen H"'

1. Anilinotriazoles as potent gamma secretase modulators.

Author

Velter AI, Bischoff FP, Berthelot D, De Cleyn M, Oehlrich D, Jaroskova L, Macdonald G, Minne G, Pieters S, Rombouts F, Van Brandt S, Van Roosbroeck Y, Surkyn M, Trabanco AA, Tresadern G, Wu T, Borghys H, Mercken M, Masungi C, and Gijsen H more...

Subjects
Amyloid Precursor Protein Secretases metabolism, Amyloid beta-Peptides chemistry, Amyloid beta-Peptides metabolism, Aniline Compounds chemical synthesis, Aniline Compounds metabolism, Animals, Brain metabolism, Drug Design, Humans, Mice, Mice, Transgenic, Protein Binding, Structure-Activity Relationship, Triazoles chemical synthesis, Triazoles metabolism, Amyloid Precursor Protein Secretases antagonists & inhibitors, Aniline Compounds chemistry, Triazoles chemistry
Abstract

The design and synthesis of a novel series of potent gamma secretase modulators is described. Exploration of various spacer groups between the triazole ring and the aromatic appendix in 2 has led to anilinotriazole 28, which combined high in vitro and in vivo potency with an acceptable drug-like profile., (Copyright © 2014 Elsevier Ltd. All rights reserved.) more...

Published
2014
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2. Rational design and synthesis of aminopiperazinones as β-secretase (BACE) inhibitors.

Author

Tresadern G, Delgado F, Delgado O, Gijsen H, Macdonald GJ, Moechars D, Rombouts F, Alexander R, Spurlino J, Van Gool M, Vega JA, and Trabanco AA

Subjects
Amyloid Precursor Protein Secretases metabolism, Binding Sites, Computer Simulation, Enzyme Activation drug effects, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Piperazines chemical synthesis, Piperazines pharmacology, Protein Structure, Tertiary, Stereoisomerism, Amyloid Precursor Protein Secretases antagonists & inhibitors, Drug Design, Enzyme Inhibitors chemical synthesis, Piperazines chemistry
Abstract

Aminopiperazinone inhibitors of BACE were identified by rational design. Structure based design guided idea prioritization and initial racemic hit 18a showed good activity. Modification in decoration and chiral separation resulted in the 40 nM inhibitor, (-)-37, which showed in vivo reduction of amyloid beta peptides. The crystal structure of 18a showed a binding mode driven by interaction with the catalytic aspartate dyad and distribution of the biaryl amide decoration towards S1 and S3 pockets., (Copyright © 2011 Elsevier Ltd. All rights reserved.) more...

Published
2011
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