【摘要】 目的设计合成一系列新型N-苯基取代的酰胺衍生物,测定其体外对S-腺苷同型半胱氨酸水解酶（SAHase）的抑制活性。方法以不同取代苯胺为起始原料,经过N-烷基化、水解、脱水环合,再分别与N-甲基异吲哚啉-2-胺或者N-甲基茚满-2-胺,以及各种胺的衍生物进行两次酰胺化反应得到目标化合物。采用荧光法考察目标化合物对SAHase的抑制活性,并探讨其初步构效关系。结果与结论共合成了25个未见文献报道的新化合物,其结构经¹H-NMR及MS谱确证。活性测试结果表明,其中,4个化合物(I₁、I₁₁、I₁₂和I₁₈)与阳性对照物3-脱氮腺苷的活性相当,具有显著抑制SAHase的活性。更多还原

【Abstract】 S-Adenosyl-L-homocysteine hydrolase（ SAHase） plays a key role in the regulation of biological transmethylation. SAHase has become an attractive target for drug design,and SAHase inhibitors have been shown to exhibit antiviral,anticancer,immunosuppressive effect. N-（ Carbamoylmethyl） glycinamide derivatives were discovered previously in our group,which exhibited good inhibitory activities. To continue our development of novel synthetic amide derivatives with improved SAHase inhibitory activity,twenty five newamide derivatives were designed and synthesized. All compounds were identified by ¹H-NMR and M S.Furthermore,the SAHase inhibitory activity of the target compounds was evaluated. The results showed that some of the target compounds exhibited SAHase inhibitory activity. Among them,four compounds( I₁,I₁₁,I₁₂ and I₁₈) exhibited potent SAHase inhibitory activity. Preliminary analysis of the structure-activity relationship revealed that the introduction of fluorine atom or chlorine atom at phenyl and ethylenediamine derivatives at the side chain were benefit for their activity. This study provides several clues for further rational design new SAHase inhibitors.更多还原