摘要
趋化因子受体CCR5是HIV-1病毒进入人体细胞的主要辅助受体,CCR5拮抗剂可作为一种靶向制剂,以防治人类HIV-1感染.目前,非肽类小分子化合物CCR5拮抗剂的研究占据主导地位.以4-氯苄氯、5-溴水杨醛为原料,通过消去、还原及溴化合成了4-溴-2-溴甲基-1-((4-溴苄基)氧)苯(中间体3),以哌啶-4-酮合成了N-烯丙基-N-(4-哌啶基)吡啶甲酰胺(中间体7),通过中间体3和7合成了一种有望用作CCR5拮抗剂的非肽类小分子化合物N-烯丙基-N-(1-(5-溴-2-((4-氯苄基)氧基)苄基)-4-哌啶基)吡啶甲酰胺,该产物有一定的生物活性,并对该产物进行了1H NMR、13C NMR、IR及MS表征.
Chemokine receptor CCR5 is a major coreceptor for HIV-1 entry into cell,CCR5 antagonists can be used as a targeting preparation in the prevention of human HIV-1 infection. At present,the peptide of small molecule compounds CCR5 antagonists research occupy the leading position. 4-bromo-2-( bromomethyl)-1-(( 4-chlorobenzyl)oxy) benzene( intermediate 3) was synthesized from 1-chloro-4-( chloromethyl) benzene and 5-bromo-2-hydroxybenzaldehyde by elimination reaction,reduction reaction and bromization. N-allyl-N-( piperidin-4-yl) picolinamide( intermediate 7) was prepared from piperidin-4-one. Further reaction of intermediate 3 with intermediate 7 gave a novel non-peptide CCR5 antagonist N-allyl-N-( 1-( 5-bromo-2-(( 4-chlorobenzyl) oxy) benzyl) piperidin-4-yl) picolinamide. The product has a certain biological activity,the compounds were characterized by1 H NMR,13 C NMR,IR and MS.
引文
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