Abstract |
Benzylidene-2,4-thiazolidinedione derivatives with substitutions on the phenyl ring at the ortho or para positions of the thiazolidinedione (TZD) group were synthesized as PTP1B inhibitors with IC50 values in a low micromolar range. Compound 3e, the lowest, bore an IC50 of 5.0 microM. In vivo efficacy of 3e as an antiobesity and hypoglycemic agent was evaluated in a mouse model system. Significant improvement of glucose tolerance was observed. This compound also significantly suppressed weight gain and significantly improved blood parameters such as TG, total cholesterol and NEFA. Compound 3e was also found to activate peroxisome proliferator-activated receptors (PPARs) indicating multiple mechanisms of action.
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Authors | Bharat Raj Bhattarai, Bhooshan Kafle, Ji-Sun Hwang, Deegendra Khadka, Sun-Myung Lee, Jae-Seung Kang, Seung Wook Ham, Inn-Oc Han, Hwangseo Park, Hyeongjin Cho |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 19
Issue 21
Pg. 6161-5
(Nov 01 2009)
ISSN: 1464-3405 [Electronic] England |
PMID | 19783142
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Obesity Agents
- Blood Glucose
- Enzyme Inhibitors
- Hypoglycemic Agents
- PPAR gamma
- Phenyl Ethers
- Thiazolidinediones
- Protein Tyrosine Phosphatase, Non-Receptor Type 1
- Ptpn1 protein, mouse
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Topics |
- Animals
- Anti-Obesity Agents
(chemical synthesis, chemistry, pharmacology)
- Binding Sites
- Blood Glucose
(metabolism)
- Catalytic Domain
- Computer Simulation
- Enzyme Inhibitors
(chemical synthesis, chemistry, pharmacology)
- Hypoglycemic Agents
(chemical synthesis, chemistry, pharmacology)
- Mice
- PPAR gamma
(antagonists & inhibitors, metabolism)
- Phenyl Ethers
(chemical synthesis, chemistry, pharmacology)
- Protein Tyrosine Phosphatase, Non-Receptor Type 1
(antagonists & inhibitors, metabolism)
- Thiazolidinediones
(chemical synthesis, chemistry, pharmacology)
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