【摘要】 为进一步研究新型抗乙肝病毒活性药物,根据活性片段拼接原理设计了一系列新型结构的去氢胆酸肟类衍生物,并预测其抗乙肝病毒活性。以去氢胆酸为原料经过酯化(或酰胺化)、肟化等反应合成8种新化合物和1种已知化合物,其中,肟类3种,肟醚类6种,均为E构型。以1H NMR、13C NMR和MS测定其结构,发现肟化反应均发生在去氢胆酸3位的羰基上。体外抗乙肝病毒活性测试结果表明部分目标产物对乙肝e型抗原HBe Ag的分泌具有抑制活性,其中,化合物2a和2c的活性较好,其半数抑制浓度IC50分别为170.36μmol/L和97.34μmol/L。初步分析化合物的构效关系,发现甲氧肟醚类化合物活性最好。研究结果为该类结构的新药的研究提供了理论依据。更多还原

【Abstract】 A series of new oxime derivatives of dehydrocholic acid( DHCA) were designed for new anti-HBV drugs according to assemble principles of active chemical fragments. The anti-HBV activities of target compounds were predicted by the Molecular Operating Environment( MOE)software.Nine target compounds with E-configuration were synthesized from DHCA by esterification( or amidation) and oximation. The structures were elucidated by1 H NMR,13 C NMR and MS data.The data revealed that oximation reactions occurred on C-3 of DHCA. The results of anti-HBV eveluation showed that a part of target compounds displayed obvious inhibitory activities to HBe Ag secretion. The IC50 on HBe Ag inhibition of compound 2 a and 2 c were respectively 170. 36 μmol/Land 97. 34 μmol/L. Preliminary structure-activity relationship study showed that methyl oxime ethers displayed better anti-HBV activities than the oximes and benzyl oxime ethers. The results provide a theoretical basis for the study of new drugs with this structure.更多还原