【作者】 谢勇；

【导师】 翁玲玲；

【作者基本信息】 四川大学 ， 药物化学， 2006， 硕士

【摘要】 病毒性疾病是严重危害人类健康的常见病和多发病。据统计，大约60％流行性传染病是由病毒感染引起的。盐酸曲金刚胺(Tromantadine hydrochloride)是德国麦氏大药厂生产一个新型的抗单纯疱疹病毒药物，该药物能使DNA和RNA病毒失活，尤其能抑制1型和2型单纯疱疹病毒，能抑制HSV(单纯疱疹病毒)诱导的细胞病变和阻断HSV细胞表面的吸收，从而抑制病毒的复制。临床上用于治疗原发性和复发性皮肤和粘膜单纯疱疹。包括唇、面部单纯疱疹及生殖器疱疹，对单纯疱疹病毒引起唇疱疹病毒疗效十分显著。国内尚无本品生产，具有较好的开发价值。作者对其制备工艺进行了大量的探索，将盐酸金刚烷胺溶于10％氢氧化钠的溶液中，在5℃以下滴加氯乙酰氯的二氯甲烷溶液，2小时后，即可得氯乙酰金刚烷胺。收率可达85％。将二甲氨基乙醇用四氢呋喃稀释，分批加入氢化钠，再加入氯乙酰金刚烷胺，加毕后，回流15小时后可得产品曲金刚胺。收率70％。溶于石油醚，通入干燥的氯化氢气体。过滤得盐酸曲金刚胺。该操作缩短了反应时间(由15小时缩短至2小时)，避免了硅胶柱层析，简化反应操作，提高了反应收率(总收率由42.4％提高至54.5％)。 盐酸曲金刚胺(5)虽然具有较强的抗病毒活性，但是其抗病毒谱窄，毒副作用较大，为了克服这些缺点，我们针对该药物的结构特征，根据生物电子等排原理设计并合成了两个目标化合物即甲基哌嗪乙酰金刚烷胺(9)和吗啉乙酰金刚烷胺(11)，均未见文献报道，以期找到比曲金刚胺疗效更显著，抗病毒谱更广，毒副作用更小的药物。其结构均经元素分析、核磁共振谱、及高分辨率质谱确证。其生物活性有待进一步研究。更多还原

【Abstract】 Virosis is a kind of disease which effects people’s health badly. Acoording to statistics about 60% epidemic diseases are caused by virus infection.Tromantadine is a new anti-herpes simplex drug which is produced by Germany pharmacyeutical company. Tromantadine can kill DNA and RNA virus, Tromantadine can especially inhibit type I and type II herpes simplex virus ,it can inhibit HSV(herpes simplex virus) induced cell change and interrupt HSV cell surface absorption . so inhibit virus reblication. Cilinically it is used to cure herpes simplex of the skin and mucous membrane, including, herpes simplex of lips and face genital organs herpes simplex. Tromantadine is very effective to lips herpes caused by herpes simplex. Tromantadine is not produced domestically, it has good research spectations. The author does a lot of work on the improvement of its manufacturing procedure.Adamantane is dissolved in 10% sodium hydroxide, chloroacetyl chloride in methylene chloride is droped to above solution at 5°C, after 2 hours, chloroacetyladmantane is got. The production rate is 85%. Dimethylaminoethanol is dissolved in THF, NaH is added to the solution, and chloroacetyladamantane is added. After 15 hours, the product of Tromantadine is got. The production rate is 70%. Tromantadine is dissolved in petro ether. Hydrogen chloride gas is introduced. After filtration, Tromantadine hydrochloride is got.The reaction time is reduced, though this process (from 15 hours to 2 hours), silica gel chromatology is not necessary in this way. The method makes the reaction simple and improves. The producton rate (total yield is improved from 42.4% to 54.5%)Although Tromantadine has relatively strong antivirus activity, its antivirus spectrum narrow, side-effects are serious, to overcome these shortcomings, according to Tromantadine’s characteristics of structures and biological electron exchange更多还原