4-[(5-甲基-2-芳基噁唑-4-基)甲氧基]-芳亚甲(苄)基取代的杂环类化合物的设计、合成与生物活性  

Design,synthesis and bioactivity of 4-[(5-methyl-2-aryloxazol-4-yl) methoxy]benzylene(benzyl)-heterocyclic compounds

作　　者：王亚楼[1] 刘星[1] 魏臻[1] 

机构地区：[1]中国药科大学药物化学教研室,江苏南京210009

出　　处：《中国药物化学杂志》2008年第2期96-100,共5页Chinese Journal of Medicinal Chemistry

摘　　要：目的设计合成具有PPARγ激动剂活性的4-[(5-甲基-2-芳基噁唑-4-基)甲氧基]-芳亚甲(苄)基取代的杂环类化合物。方法以丁二酮单肟为原料,经与(取代)苯甲醛环合、氯化得到氯甲基唑衍生物,再与对羟基苯甲醛或香兰醛缩合,最后与各种杂环进行Knoevenagel反应得到目标化合物。结果合成了12个未见文献报道的新化合物,并利用元素分析、IR和1H-NMR确证了结构。结论初步活性试验显示,化合物13和16与PPARγ具有一定的结合活性,但是其抑制率均略小于50%,表明其IC50值可能略大于10μmol·L-1。Aim To design and synthesize 4- [ （5-methyl-2-aryloxazol-4-yl） methoxy ] benzylene （ benzyl ）-hete- rocyclic compounds for PPAR7 activity. Methods The butanedione rnonoxirne was reacted with（substituted） benzaldehyde via cyclization and chlorination to give 4-（chloromethyl）-5-methyl-2-aryloxazole derivatives, which was condensed with 4-hydroxybenzaldehyde or vanillin, and then followed by Knoevenagel reaction with the heterocyclic compounds to give the target compounds. Results 12 Novel compounds were synthesized. All the compounds were characterized by ^1H-NMR, IR, and elemental analysis. Conclusion The preliminary test show that the compounds 13 and 16 has PPAR7 activity each, but the inhibition rate is slightly less than 50 %, indicating ICs0 values is bit larger than 10 μmol·L^- 1 each.

关 键 词：4-[(5-甲基-2-芳基噁唑-4-基)甲氧基]-芳亚甲(苄)基取代的环类化合物 合成 PPAR7活性 胰岛素 增敏剂 

分 类 号：R914[医药卫生—药物化学]