目的 合成苯并咪唑類衍生物并研究其對(duì)X連鎖凋亡抑制蛋白的抑制活性。方法 以1-Boc-2-氨基甲酰吡咯烷為起始原料，依次通過(guò)硫代、烷基化、環(huán)合、還原、氧化、環(huán)合、脫保護(hù)、縮合、脫保護(hù)等11步反應(yīng)合成苯并咪唑類衍生物，采用熒光偏振法對(duì)目標(biāo)化合物進(jìn)行了體外XIAP抑制活性測(cè)試。結(jié)果 合成得到4個(gè)目標(biāo)產(chǎn)物，其結(jié)構(gòu)經(jīng)¹H-NMR和ESI-MS確證?；钚詼y(cè)試結(jié)果顯示，所設(shè)計(jì)化合物均具有一定的XIAP抑制活性，其中，10a~10c的IC₅₀為1.2~2.7 μmol/L。結(jié)論 苯并咪唑芳環(huán)上電子效應(yīng)及NH基團(tuán)為重要活性位點(diǎn)，值得進(jìn)一步研究。

Objective To synthesize benzimidazole derivatives and study the inhibitory activities of benzimidazole against X inhibitor of apoptosis proteins (XIAP). Methods 1-Boc-L-prolinamide was used as the starting materials to synthesize benzimidazole derivatives by a eleven-step route reaction of sulpho-reaction, alkylation, cyclized, reduction, oxidation, cyclized, de-protection, condensation, and de-protection, etc. The XIAP inhibitor activities were tested with fluorescence polarization method in vitro. Results Four novel compounds were synthesized and their structures were confirmed by ¹H-NMR and ESI-MS. The activity experiments showed that the target compounds exhibited potent IAP inhibitor activities. Among them, IC₅₀ of compounds 10a-10c were 1.2-2.7 μmol/L. Conclusion The electronic effect and NH group of benzimidazole ring is the important active site, which merits further study.