P3 cap modified Phe-Ala series BACE inhibitors

With the aim of reducing molecular weight and adjusting log D value of BACE inhibitors to more favorable range for BBB penetration and better bioavailability, we synthesized and evaluated several series of P3 cap modified BACE inhibitors obtained via replacement of the P3 NHBoc moiety as seen in 3 w...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2004-01, Vol.14 (1), p.245-250
Main Authors: Chen, Shu-Hui, Lamar, Jason, Guo, Deqi, Kohn, Todd, Yang, Hsiu-Chiung, McGee, James, Timm, David, Erickson, Jon, Yip, Yvonne, May, Patrick, McCarthy, James
Format: Article
Language:English
Subjects:
Amyloid Precursor Protein Secretases
Aspartic Acid Endopeptidases
Biological and medical sciences
Cell Line
Dipeptides - chemistry
Dipeptides - pharmacology
Endopeptidases - metabolism
Humans
Medical sciences
Neuropharmacology
Pharmacology. Drug treatments
Protease Inhibitors - chemistry
Protease Inhibitors - pharmacology
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
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Summary:With the aim of reducing molecular weight and adjusting log D value of BACE inhibitors to more favorable range for BBB penetration and better bioavailability, we synthesized and evaluated several series of P3 cap modified BACE inhibitors obtained via replacement of the P3 NHBoc moiety as seen in 3 with other polar functional groups such as amino, hydroxyl and fluorine. Several promising inhibitors emerging from this P3 cap SAR study (e.g., 15 and 19) demonstrated good enzyme inhibitory potencies (BACE-1 IC 50
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2003.09.085