扎那米韦

扎那米韦

CAS号:139110-80-8
英文名:zanamivir
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化合物简介
Zanamivir INN is a neuraminidase inhibitor used in the treatment and prophylaxis of influenza caused by influenza A and B viruses. It was developed by the Australian biotech firm Biota Holdings. It was licensed to Glaxo in 1990 and approved in the US in 1999, only for use as a treatment for influenza. In 2006, it was approved for prevention of influenza A and B. Zanamivir was the first neuraminidase inhibitor commercially developed. It is currently marketed by GlaxoSmithKline under the trade name Relenza as a powder for oral inhalation.
基本信息
编号系统
物化性质
生产方法及用途
生产方法
将5-乙酰氨基-4,7,8,9-四-O-乙酰基-2,3,5-三脱氧-D-甘油基-D-半乳糖壬-2-烯吡喃糖醇溶于苯和甲醇中,在室温和搅拌下,滴加BF3Et2O,加入乙酸乙酯,依次用饱和碳酸氢钠、水洗、浓缩,加入水和乙酸,搅拌。加入乙酸乙酯,用5%碳酸氢钠、水洗、浓缩。得到的物质硅胶柱层析,得4位O-乙酰基水解产物。该化合物溶于无水二氯甲烷和吡啶,滴加含三氟甲磺酸酐的二氯甲烷溶液,搅拌。减压浓缩至干,得到的物质溶于含叠氮钠和四丁基硫酸氢铵的二甲基甲酰胺溶液,在室温搅拌。减压浓缩至干,得到的物质加入乙酸乙酯和水,分出有机层,水洗、干燥、浓缩。得到的物质硅胶柱层析,得4位叠氮化产物。该化合物溶于吡啶,在室温用硫化氢鼓泡,通入氮气。减压蒸出吡啶,得到的物质硅胶柱层析,得4位还原为氨基的产物。在冰浴冷却下,将该化合物加到含犛甲基硫脲的水中,反应后,放入离子交换树脂柱中,先用冷水洗, 再用氨水展开。得到的流出液经减压浓缩至干,得到的物质用硅胶柱层析,得扎那米韦。
用途
用于治疗A型和B型流感。神经氨酸酶抑制剂。该品通过抑制流感病毒的神经氨酸酶,从而改变了流感病毒在感染细胞内的聚集和释放。适用于流感症状出现不到2天的成人或12岁以上青少年的A型或B型流感病毒引起的无并发症的急件感染的治疗。
上游原料
(1S,2R)-1-((2R,3R)-3-acetamido-6-(benzoyloxy)-6-(methoxycarbonyl)-3,6-dihydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate N-氰基扎那米韦胺三乙酸酯甲酯 甲基(3aR,4R,7aR)-2-甲基-4-[(1S,2R)-1,2,3-三乙酰氧基丙基]-3a,7a-二氢-4H-吡喃并[3,4-d][1,3]恶唑-6-羧酸酯 (5R,6R,7R,8R,E)-methyl 5-acetamido-7,8,9-tris(benzyloxy)-2,6-bis((tert-butyldimethylsilyl)oxy)non-2-enoate (1S,2R)-1-((2R,3R,4S)-3-acetamido-4-((Z)-2,3-bis(tert-butoxycarbonyl)guanidino)-6-(methoxycarbonyl)-3,4-dihydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate (2R,3R,4S)-3-acetamido-4-((Z)-2,3-bis(tert-butoxycarbonyl)guanidino)-2-((1R,2R)-1,2,3-trihydroxypropyl)-3,4-dihydro-2H-pyran-6-carboxylic acid N-((4R,5R,6R,7R)-6,7,8-tris(benzyloxy)-5-((tert-butyldimethylsilyl)oxy)oct-1-en-4-yl)acetamide methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-β-D-galacto-non-2-ulopyranosyl chloride N-((3R,4R,5R,6R)-5,6,7-tris(benzyloxy)-4-((tert-butyldimethylsilyl)oxy)-1-oxoheptan-3-yl)acetamide N-((4R,5R,6S,7R)-6,7,8-tris(benzyloxy)-5-hydroxyoct-1-en-4-yl)acetamide 5-acetamido-4-guanidino-6-(1,2,3-triacetoxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate 1H-吡唑-1-甲脒盐酸盐 5-乙酰氨基-7,8,9-O-三乙酰基-2,6-脱水-4-叠氮-3,4,5-三脱氧-D-甘油-D-半乳-2-壬烯酸甲酯 (4R,5R)-tert-butyl 4-allyl-2,2-dimethyl-5-((1S,2R)-1,2,3-tris(benzyloxy)propyl)oxazolidine-3-carboxylate (4R,5R)-tert-butyl 4-allyl-5-((2S,3S)-3-(hydroxymethyl)oxiran-2-yl)-2,2-dimethyloxazolidine-3-carboxylate (4R,5R)-tert-butyl 4-allyl-2,2-dimethyl-5-((1R,2R)-1,2,3-trihydroxypropyl)oxazolidine-3-carboxylate (4R,5S)-tert-butyl 4-allyl-5-((E)-3-((4-methoxybenzyl)oxy)prop-1-en-1-yl)-2,2-dimethyloxazolidine-3-carboxylate (4R,5S)-tert-butyl 4-allyl-5-((E)-3-hydroxyprop-1-en-1-yl)-2,2-dimethyloxazolidine-3-carboxylate methyl 5-acetamido-2,7,8,9-tetra-O-acetyl-3,4,5-trideoxy-D-manno-2-nonulopyranosonate tert-butyl ((4R,5S,E)-5-hydroxy-8-((4-methoxybenzyl)oxy)octa-1,6-dien-4-yl)carbamate N-Acetyl-S-methylisothiourea (4S,5R,E)-1-((4-methoxybenzyl)oxy)-5-nitroocta-2,7-dien-4-ol Methyl 5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-talo-non-2-enonate 氨基亚氨基甲烷磺酸 (2R,3R,4S)-3-乙酰氨基-4-乙酰氧基-2-((1R,2R)-1,2,3-三乙酰氧基丙基)-3,4-二氢-2H-吡喃-6-羧酸甲酯 5-acetylamino-2,6-anhydro-4-cyanoamino-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enonic acid 扎那米韦中间体2 methyl (5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-enpyranosyl)onate 扎那米韦 Neu5Ac methyl ester