Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors

Guided by X-ray crystallography, we have extended the structure–activity relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor ( 1) and more potent and equally selective (>20-fold selectivity over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identifie...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2004-11, Vol.14 (22), p.5543-5546
Main Authors: Zhao, Hongyu, Liu, Gang, Xin, Zhili, Serby, Michael D., Pei, Zhonghua, Szczepankiewicz, Bruce G., Hajduk, Philip J., Abad-Zapatero, Cele, Hutchins, Charles W., Lubben, Thomas H., Ballaron, Stephen J., Haasch, Deanna L., Kaszubska, Wiweka, Rondinone, Cristina M., Trevillyan, James M., Jirousek, Michael R.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carboxylic Acids - chemical synthesis
Carboxylic Acids - chemistry
Carboxylic Acids - pharmacology
Cell permeable
Cercopithecus aethiops
COS Cells
Crystallography, X-Ray
Isoxazoles - chemical synthesis
Isoxazoles - chemistry
Isoxazoles - pharmacology
Medical sciences
Miscellaneous
Models, Molecular
Molecular Structure
Pharmacology. Drug treatments
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatases - antagonists & inhibitors
PTP1B
Selective
Structure-Activity Relationship
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Summary:Guided by X-ray crystallography, we have extended the structure–activity relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor ( 1) and more potent and equally selective (>20-fold selectivity over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identified. Inhibitor 7 demonstrated good cellular activity against PTP1B in COS 7 cells. Guided by X-ray crystallography, we have extended the structure–activity relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor ( 1) and more potent and equally selective (>20-fold selectivity over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identified. Inhibitor 7 demonstrated good cellular activity against PTP1B in COS 7 cells.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2004.08.063