title: Novel thiazolidinedione derivatives with anti-obesity effects: dual action as PTP1B inhibitors and PPAR-γ activators.
abstract: Benzylidene-2,4-thiazolidinedione derivatives with substitutions at both the ortho and para-positions of the phenyl group were synthesized as PTP1B inhibitors with IC(50) values in a low micromolar range. Compound 18l, the lowest, bore an IC(50) of 1.3 μM. In a peroxisome proliferator-activated receptor-γ (PPAR-γ) promoter reporter gene assay, 18l was found to activate the transcription of the reporter gene with potencies comparable to those of troglitazone, rosiglitazone, and pioglitazone. In vivo efficacy of 18l as an anti-obesity and hypoglycemic agent was evaluated in a mouse model system. Compound 18l significantly suppressed weight gain and significantly improved blood parameters such as TG, total cholesterol and NEFA without overt toxic effects.
authors.affiliation: Department of Chemistry, Inha University, Incheon 402-751, Republic of Korea.
authors.forename: Bharat Raj
authors.initials: BR
authors.lastname: Bhattarai
authors.forename: Bhooshan
authors.initials: B
authors.lastname: Kafle
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Hwang
authors.forename: Seung Wook
authors.initials: SW
authors.lastname: Ham
authors.forename: Keun-Hyeung
authors.initials: KH
authors.lastname: Lee
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.forename: Inn-Oc
authors.initials: IO
authors.lastname: Han
authors.forename: Hyeongjin
authors.initials: H
authors.lastname: Cho
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007004:Hypoglycemic Agents / Q000494:pharmacology; D051379:Mice; D047495:PPAR gamma / Q000819:agonists*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D045162:Thiazolidinediones / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D019440:Anti-Obesity Agents; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D014280:Triglycerides; D002784:Cholesterol; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1