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Design and synthesis of bicyclic acetals as Beta Secretase (BACE1) inhibitors.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2017 Oct 01; Vol. 25 (19), pp. 5077-5083. Date of Electronic Publication: 2017 Mar 18. - Publication Year :
- 2017
-
Abstract
- Taking advantage of the structural similarity between aspartic proteases, small-molecule peptidomimetic inhibitors that already showed activity towards Secreted Aspartic Protease 2 as anti-Candida agents and HIV protease inhibitors were exploited as potential BACE1 inhibitors. A focused library of 6,8-dioxa-3-azabicyclo[3.2.1]-octane peptidomimetic scaffolds was synthesized and assayed towards BACE1 enzyme, resulting in the identification of a thiolactam-containing hit compound possessing IC <subscript>50</subscript> in the low micromolar range, and confirming the bicyclic acetal portion as a potential transition state analogue in the interaction with catalytic aspartic acid residues.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Acetals chemical synthesis
Acetals chemistry
Acetals pharmacology
Amino Acid Sequence
Amyloid Precursor Protein Secretases chemistry
Amyloid Precursor Protein Secretases metabolism
Aspartic Acid Endopeptidases chemistry
Aspartic Acid Endopeptidases metabolism
Azabicyclo Compounds chemical synthesis
Drug Design
Enzyme Inhibitors chemical synthesis
HIV Protease Inhibitors chemistry
HIV Protease Inhibitors pharmacology
Humans
Molecular Docking Simulation
Peptidomimetics chemical synthesis
Sequence Alignment
Amyloid Precursor Protein Secretases antagonists & inhibitors
Aspartic Acid Endopeptidases antagonists & inhibitors
Azabicyclo Compounds chemistry
Azabicyclo Compounds pharmacology
Enzyme Inhibitors chemistry
Enzyme Inhibitors pharmacology
Peptidomimetics chemistry
Peptidomimetics pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 25
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 28359674
- Full Text :
- https://doi.org/10.1016/j.bmc.2017.03.030