Novel pyrazolopyrimidine derivatives as GSK-3 inhibitors

A series of [1-aryl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]arylhydrazones were discovered as novel inhibitors glycogen synthase kinase-3 (GSK-3). Based on initial modeling a detailed SAR was constructed. Modification of the interior binding aryl ring (Ar(1)) determined this to be a tight binding region wi...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2004-05, Vol.14 (9), p.2121-2125
Main Authors: PEAT, Andrew J, BOUCHERON, Joyce A, WANG, Tony Y, ZHOU, Huiqiang Q, THOMSON, Stephen A, DICKERSON, Scott H, GARRIDO, Dulce, MILLS, Wendy, PECKHAM, Jennifer, PREUGSCHAT, Frank, SMALLEY, Terrence, SCHWEIKER, Stephanie L, WILSON, Jayme R
Format: Article
Language:English
Subjects:
Biological and medical sciences
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Glycogen Synthase Kinase 3 - antagonists & inhibitors
Medical sciences
Miscellaneous
Models, Molecular
Pharmacology. Drug treatments
Pyrazoles - chemistry
Pyrimidines - chemistry
Pyrimidines - pharmacology
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Summary:A series of [1-aryl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]arylhydrazones were discovered as novel inhibitors glycogen synthase kinase-3 (GSK-3). Based on initial modeling a detailed SAR was constructed. Modification of the interior binding aryl ring (Ar(1)) determined this to be a tight binding region with little room for modification. As predicted from the model, a large variety of modifications could be incorporated into the hydrazone aryl ring. This work led to GSK-3 inhibitors in the low nano-molar range.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2004.02.036