کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1398115 | 1501206 | 2008 | 18 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Tryptophan-containing dipeptide derivatives as potent PPARγ antagonists: Design, synthesis, biological evaluation, and molecular modeling Tryptophan-containing dipeptide derivatives as potent PPARγ antagonists: Design, synthesis, biological evaluation, and molecular modeling](/preview/png/1398115.png)
The discovery of peroxisome proliferator-activated receptor γ (PPARγ) antagonists (also termed “selective PPARγ modulators, SPPARγM”) is now of a great interest in the treatment of diabetes and obesity. The structure of compound 1a (G3335, Fig. 1), a novel class of PPARγ antagonist, is entirely different from that of other reported PPARγ antagonists. A series of 35 novel analogues (1b–l, 9a–d, 13a–t) were designed, synthesized and evaluated against the agonistic effects exerted by rosiglitazone. These results indicated that most functional groups of 1a were conserved, and six new compounds (1b, 1c, and 9a–d) exhibited strong PPARγ antagonistic activities (IC50 values of 5.2–25.8 μM) against 10 μM rosiglitazone in the promotion of the PPARγ–LBD–CBP (ligand-binding domain and cAMP-response-element binding protein) interaction as investigated by yeast two-hybrid technology based assay. Molecular modeling studies for compounds 1a–d, 1h, 9c–d, and 13a were also presented.
A series of dipeptide derivatives were synthesized and evaluated. SARs were explored at atomic level and the influence of the two chiral centres was investigated.Figure optionsDownload as PowerPoint slide
Journal: European Journal of Medicinal Chemistry - Volume 43, Issue 12, December 2008, Pages 2699–2716