Department of Chemistry, Inha University, Incheon 402-751, Republic of Korea.
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6161-5. doi: 10.1016/j.bmcl.2009.09.020. Epub 2009 Sep 10.
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.
苯并亚甲基-2,4-噻唑烷二酮衍生物具有噻唑烷二酮（TZD）基团在苯基环的邻位或对位上的取代基，被合成为 PTP1B 抑制剂，其 IC50 值在低微摩尔范围内。化合物 3e 的 IC50 值最低，为 5.0 μM。作为一种抗肥胖和降血糖药物，3e 在小鼠模型系统中的体内疗效进行了评估。观察到葡萄糖耐量显著改善。该化合物还显著抑制体重增加，并显著改善 TG、总胆固醇和 NEFA 等血液参数。还发现化合物 3e 激活过氧化物酶体增殖物激活受体 (PPARs)，表明具有多种作用机制。
