A novel series of potent γ-secretase inhibitors based on a benzobicyclo[4.2.1]nonane core

[Display omitted] A new series of γ-secretase inhibitors was developed from an in-house screening hit based on a benzobicyclo[4.2.1]nonane core. Lead optimisation studies led to the development of a series of potent inhibitors and in vivo efficacy was demonstrated.

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 15; no. 2; pp. 373 - 378
Main Authors:	Lewis, Stephen J., Smith, Adrian L., Neduvelil, Joseph G., Stevenson, Graeme I., Lindon, Matthew J., Jones, A. Brian, Shearman, Mark S., Beher, Dirk, Clarke, Earl, Best, Jonathan D., Peachey, James E., Harrison, Timothy, Castro, J. Luis
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 17-01-2005 Elsevier
Subjects:	Alkanes - chemical synthesis Alkanes - pharmacology Alzheimer Disease - drug therapy Alzheimer Disease - metabolism Amides - chemistry Amines - chemistry Amyloid Precursor Protein Secretases Animals Aspartic Acid Endopeptidases Biological and medical sciences Brain - drug effects Brain - metabolism Endopeptidases - metabolism Heterocyclic Compounds - chemistry Medical sciences Mice Neuropharmacology Pharmacology. Drug treatments Protease Inhibitors - chemical synthesis Protease Inhibitors - pharmacology Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Structure-Activity Relationship γ-Secretase inhibitors γ-Secretase inhibitors Imidazole derivatives Alzheimer disease Nitrogen heterocycle Morpholine derivatives Pyrrolidine derivatives Pyridine derivatives Thiophene derivatives Structure activity relation Piperidine derivatives Degenerative disease Aspartic endopeptidases Aromatic compound Inhibition Chemical synthesis Nervous system diseases Sulfonamide Enzyme Aliphatic compound Rodentia Benzene derivatives Oral administration Enzyme inhibitor Aminoether Antialzheimer agent Tricyclic compound In vitro Amyloid precursor protein Cerebral disorder Peptidases In vivo Vertebrata Chemotherapy Sulfur heterocycle Experimental disease Mammalia Treatment Mouse Animal Central nervous system disease Hydrolases Carboxamide Piperazine derivatives
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Summary:	[Display omitted] A new series of γ-secretase inhibitors was developed from an in-house screening hit based on a benzobicyclo[4.2.1]nonane core. Lead optimisation studies led to the development of a series of potent inhibitors and in vivo efficacy was demonstrated.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2004.10.062