Structure based design of a series of potent and selective non peptidic PTP-1B inhibitors

A series of benzotriazole phenyldifluoromethylphosphonic acids were found to be potent PTP-1B inhibitors. Molecular modeling on the X-ray crystal structure of the lead structure led to the design of potent PTP-1B inhibitors that show moderate selectivity against TC-PTP, a very closely related protei...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 14; no. 4; pp. 1043 - 1048
Main Authors:	LOU, Cheuk K, BAYLY, Christopher I, QINGPING WANG, SKOREY, Kathryn, WADDLETON, Deena, PAYETTE, Paul, RAMACHANDRAN, Chidambaram, KENNEDY, Brian P, SCAPIN, Giovana, GAUTHIER, Jacques Yves, CHUN SING LI, THERIEN, Michel, ASANTE-APPIAH, Ernest, CROMLISH, Wanda, BOIE, Yves, FORGHANI, Farnaz, DESMARAIS, Sylvie
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier 23-02-2004
Subjects:	Animals Biological and medical sciences Cell Line Cell Survival - drug effects Crystallography, X-Ray Drug Design Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology General and cellular metabolism. Vitamins Insecta Medical sciences Mice Mice, Knockout Models, Molecular Molecular Structure Organophosphorus Compounds - chemical synthesis Organophosphorus Compounds - chemistry Organophosphorus Compounds - pharmacology Pharmacology. Drug treatments Protein Tyrosine Phosphatase, Non-Receptor Type 1 Protein Tyrosine Phosphatases - antagonists & inhibitors Structure-Activity Relationship Benzotriazole derivatives Enzyme Active site Phosphonic acids Phosphoric monoester hydrolases Enzyme inhibitor Quinoline derivatives Non peptide compound Esterases Inhibitor enzyme complex Selectivity Modeling Phosphorus Organic compounds Geminal compound Structure activity relation Hydrolases Benzenic compound Fluorine Organic compounds Chemical synthesis Protein-tyrosine-phosphatase Crystalline structure
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Summary:	A series of benzotriazole phenyldifluoromethylphosphonic acids were found to be potent PTP-1B inhibitors. Molecular modeling on the X-ray crystal structure of the lead structure led to the design of potent PTP-1B inhibitors that show moderate selectivity against TC-PTP, a very closely related protein tyrosine phosphatase.
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.2003.11.076