1639899-90-3Relevant articles and documents
Structure-based design, synthesis, PPAR-γ activation, and molecular docking of N-substituted phthalimides
Xiao, Bin,Wang, Shumin,She, Zhanfei,Cao, Qingfeng,Zhao, Na,Tian, Xiangrong,Su, Yixin
, p. 1628 - 1634 (2017)
N-substituted phthalimides showed peroxisome proliferator-activated receptors-γ activation in rat liver epithelial Ac2F cells in our previous study. In order to explore better peroxisome proliferator-activated receptors-γ agonists, new N-substituted phthalimide derivatives were designed and synthesized based on a pharmacophore study of natural peroxisome proliferator-activated receptors-γ agonist paecilocin A and synthetic leads. Peroxisome proliferator-activated receptors-γ activation by the new derivatives was evaluated using rat liver epithelial Ac2F cells at a concentration of 10 μM (same as previous study). All the new derivatives showed comparable or better activities than that of rosiglitazone, in which 3-hydroxy-N-(p-methoxy-phenethyl) phthalimide (compound 6) appeared as the best. Molecular docking suggested that the free hydroxyl group on the phthalimide head, a proper hydrophobic tail including a phenyl linker, were beneficial for peroxisome proliferator-activated receptors-γ activation. These N-substituted phthalimide derivatives are valuable as scaffolds for new peroxisome proliferator-activated receptors-γ agonists.
Synthesis of PPAR-γ activators inspired by the marine natural product, paecilocin A
Xiao, Bin,Su, Mingzhi,Kim, Eun La,Hong, Jongki,Chung, Hae Young,Kim, Hyung Sik,Yin, Jun,Jung, Jee H.
, p. 926 - 939 (2014/03/21)
A series of N-substituted phthalimide derivatives were synthesized based on a pharmacophore study of paecilocin A (a natural PPAR-γ agonist) and synthetic leads. The introduction of hydrophilic and hydrophobic groups to the phthalimide skeleton yielded compounds 3-14. Compound 7 showed significant PPAR-γ activation in a luciferase assay using rat liver Ac2F cells. Docking simulations showed that a free hydroxyl group on the phthalimide head and a suitable hydrophilic tail, including a phenyl linker, were beneficial for PPAR-γ activation. Compound 7 and rosiglitazone concentration-dependently activated PPAR-γ with EC50 values of 0.67 μM and 0.028 μM, respectively. These phthalimide derivatives could be further investigated as a new class of PPAR-γ ligands.
