Format

Send to

Choose Destination
See comment in PubMed Commons below
Bioorg Med Chem. 2006 Dec 15;14(24):8210-8. Epub 2006 Sep 28.

Probing the physicochemical and structural requirements for glycogen synthase kinase-3alpha inhibition: 2D-QSAR for 3-anilino-4-phenylmaleimides.

Author information

1
Department of Medicinal Chemistry, School of Pharmacy, University of Mississippi, MS 38677-1848, USA.

Abstract

Glycogen synthase kinase-3alpha (GSK-3alpha) was recently found to be an attractive target for the treatment of Alzheimer's disease due to its dual action in the formation of both amyloid plaques and neurofibrillary tangles. It is also a viable target for many other diseases, such as type 2 diabetes. Reported herein is a 2D-QSAR exploration of the physicochemical (hydrophobic, electronic, and steric) and structural requirements among 3-anilino-4-phenylmaleimides toward GSK-3alpha binding. Using Fujita-Ban and Hansch QSAR analysis, electronic and steric interactions at the 4-phenyl ring and hydrophobic interactions at the 3-anilino ring are shown to be crucial. Analysis of the 4-phenyl ring of these compounds using common aromatic substituent constants showed electron-withdrawing and bulky ortho substituents as imperative for GSK-3alpha inhibition.

PMID:
17010615
DOI:
10.1016/j.bmc.2006.09.021
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center