N-哌啶基苯甲酰氨类CCR5拮抗剂的合成及表征

Synthesis and structural characterization of N-Piperidine benzamides CCR5 antagonists

以5-溴水杨醛和4-氯苄氯为原料,通过消去、还原及溴化反应合成4-溴-2-溴甲基-1-((4-溴苄基)氧)苯(中间体Ⅲ),以1-苄基-4-哌啶酮合成2-氯-N-烯丙基-N-(4-哌啶基)苯甲酰胺(中间体Ⅶ),通过中间体Ⅲ和中间体Ⅶ合成新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)-2-氯苯甲酰氨,作为趋化因子受体(CCR5)拮抗剂,经GTPγS活性检测,其半抑制率IC50为(5.35±0.3)nmol/L,并对该产物进行1H NMR、13C NMR、IR及MS表征。

The 4-bromo-2-（ bromomethyl）-1-（（ 4-chlorobenzyl） oxy） benzene（ intermediate Ⅲ） was synthesized from 1-chloro-4-（ chloromethyl） benzene and 5-bromo-2-hydroxybenzaldehyde by elimination reaction,reduction reaction and bromization. N-allyl-2-chloro-N-（ piperidin-4-yl） benzamide was prepared from 1-benzylpiperidin-4-one. Further reaction of intermediate Ⅲ with intermediate Ⅶgave a novel non-peptide CCR5 antagonist N-allyl-N-（ 1-（ 5-bromo-2-（（ 4-chlorobenzyl） oxy） benzyl） piperidin-4-yl）-2-chlorobenzamide. By detecting the activity of GTPγS,the hemi-inhibitory concentration（ IC50） was（ 5. 35 ± 0. 3） nmol/L. The products exhibit certain bioactivities. In addition,the compounds are characterized by1 H NMR,13 C NMR,IR and MS.