神经氨酸酶抑制剂帕拉米韦的合成及其抗禽流感病毒药效  

Synthesis and anti-influenza efficacy evaluation of peramivir

作　　者：陈建新[1] 陈良柱[1,2] 刘雅红[1] 韦兰萍[1] 方炳虎[1,2] 

机构地区：[1]华南农业大学兽医学院,广州510642 [2]广东大华农动物保健品股份有限公司,新兴527439

出　　处：《中国抗生素杂志》2009年第8期475-478,共4页Chinese Journal of Antibiotics

基　　金：广东省农业攻关计划项目(2006B20801001)

摘　　要：目的改进神经氨酸酶抑制剂帕拉米韦合成方法,提高其反应收率,确定其对人工感染禽流感病毒小鼠的防治效果、适宜剂量及给药方式。方法以文斯内酰胺和2-乙基丁醛为主要原料,经催化开环、氨基保护、环化加成等步骤合成了帕拉米韦,通过1H NMR,13C NMR及MS等方法确定了中间体及目标化合物的结构。考察不同剂量和给药方式的帕拉米韦预防及治疗人工感染H9N2亚型禽流感病毒小鼠的药效。结果合成帕拉米韦的总收率为52.7%,较文献提高了28%。帕拉米韦对感染小鼠的保护效果具有剂量和治疗时间依赖性。40mg/kg剂量的帕拉米韦一次性肌注,对感染小鼠的保护率为100%。感染病毒后2d内给药疗效较好。结论帕拉米韦对感染禽流感病毒小鼠具有显著的防治效果,肌注效果较好。Objective The purpose of this paper was to raise yield of peramivir by improving synthesis processes and to define adequate dosage and administration pathway for preventing and curing mice infected by avian influenza viruses. Methods Peramivir was synthesized with 2-azabicyclo [ 2, 2, 1 ] hept-5-en-3-one and 2-ethyl butylaldehyde as starting materials and through multi-steps reactions including amide hydrolysis, amino group protection and addition reaction. Structures of the synthetic compounds were identificated by 1H-NMR, 13C-NMR and MS. The efficacies of different dosages and administration pathways of peramivir in mice infected with H9N2 influenza viruses were investigated. Results The total yield of synthesizing peramivir was 52.7%. The efficacies of peramivir preventing lethality in mouse influenza models depended on dosage, administration pathway and treatment time-point. A single intramuscular injection of peramivir at 40mg/kg dosage completely prevented lethality in H9N2 influenza models. IM administration of 40 mg/kg single dose of peramivir during 48 h post-infection gave better protection againt lethality （survival rate≥7/10）, whereas, the survival rate of IM administration of peramivir 60h post-infection sharply dropped out to 4/10. Conclusions IM administration of peramivir had pronounced effectiveness in preventing lethality of mice infected by H9N2 avian influenza viruses.

关 键 词：帕拉米韦 合成 禽流感病毒 药效 

分 类 号：R978.7[医药卫生—药品]