Design, synthesis, and biological activity of novel PPARgamma ligands based on rosiglitazone and 15d-PGJ2.
Design, synthesis, and biological activity of novel PPARgamma ligands based on rosiglitazone and 15d-PGJ2.
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DOI：
10.1016/j.bmcl.2005.01.074
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发表时间：
2005-03
影响因子：
2.7
通讯作者：
Shinya Usui;Takayoshi Suzuki;Y. Hattori;Kazuma Etoh;Hiroki Fujieda;M. Nishizuka;M. Imagawa;H. Nakagawa
中科院分区：
文献类型：
--
作者：
Shinya Usui;Takayoshi Suzuki;Y. Hattori;Kazuma Etoh;Hiroki Fujieda;M. Nishizuka;M. Imagawa;H. Nakagawa
为了开发新型的PPARγ配体，我们根据罗格列酮和15d-PGJ2的结构设计了13个3-{4-(2-氨基乙氧基)苯基}丙酸衍生物。在这些化合物中，化合物9在结合试验和前脂肪细胞分化试验中被发现与罗格列酮一样有效。分子模拟表明，9的壬基与疏水氨基酸残基相互作用，构成了PPARγ蛋白的疏水区，15d-PGJ2的烷基链可能位于该区域。
To develop novel PPARγ ligands, we synthesized thirteen 3-{4-(2-aminoethoxy)phenyl}propanoic acid derivatives, which are designed based on the structures of rosiglitazone and 15d-PGJ2. Among these compounds, compound 9 was found to be as potent as rosiglitazone in a binding assay and a preadipocyte differentiation test. Molecular modeling suggested that the nonyl group of 9 interacted with hydrophobic amino acid residues constructing the hydrophobic region of PPARγ protein where the alkyl chain of 15d-PGJ2is expected to be located.