链接由说说无妨:
抗乙肝病毒一类新药盐酸艾咪朵尔获Ⅰ/Ⅱ期临床试验批件
来源：科研处 日期：2008-11-21 由我校宫平教授课题组研制的抗乙肝病毒一类新药盐酸艾咪朵尔原料及片剂，于2008年9月22日获得国家食品药品监督管理局颁发的药物Ⅰ/Ⅱ期临床试验批件。
宫平教授课题组在对5-羟基-1H-吲哚-3-羧酸乙酯类化合物进行抗流感病毒研究的过程中，发现该类化合物对乙肝病毒具有显著的抑制作用，并对其进行深入研究，得到体内外抗病毒药效强、毒性低的化合物，经国家药典委员会核准，命名为盐酸艾咪朵尔。课题组自2003年起，按照《药品注册管理办法》及有关技术指导原则的要求，对盐酸艾咪朵尔进行一类抗乙肝病毒药物的研究与开发。目前，已完成其临床前研究，并于2008年9月22日获得国家食品药品监督管理局颁发的化学药物1.1类Ⅰ/Ⅱ期临床试验批件(原料：2008L09230，片剂：2008L09232)。
我校已将包括盐酸艾咪朵尔在内的5-羟基-1H-吲哚-3-羧酸乙酯类化合物申请了中国及世界发明专利(国内申请号：200510054663.2，国际申请号：PCT/CN2005/000301)，其中在韩国已获得专利授权，其他国家已进入实质审查。
我校已于2008年3月18日将该新药以4000万元的价格转让给天津金泰源生物医药科技开发有限公司，此次转让仅包括该新药的国内专利权。
该新药若开发成功上市，将为临床上乙型肝炎的治疗提供新型、有效且价格适中的化学合成类抗病毒药物。由于盐酸艾咪朵尔抗乙肝病毒作用机制独特新颖，高效低毒，并且以目前的原料药合成成本计，其制剂价格约为拉米夫定的二分之一，普通消费者即可承担，因此估计上市后，可成为治疗乙型肝炎的一线药物，将占有近三分之一的抗乙肝病毒药物市场，每年销售额估计可达3亿元人民币，产生巨大的经济效益；同时，可提升和改善广大乙肝患者的生活质量，兼具显著的社会效益。
国际申请号：PCT/CN2005/000301 http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7960427.PN.&OS=PN/7960427&RS=PN/7960427
FIELD OF THE INVENTION
The present invention relates to a new series of 5-hydroxyindole-3-carboxylate derivatives, a pharmaceutical composition comprising the 5-hydroxyindole-3-carboxylate derivative as an effective constituent, their uses in the preparation ofmedicament for the treatment and/or prophylaxis of virus infection, especially Hepatitis B virus (HBV) infection and Human immunodeficiency virus (HIV) infection.
BACKGROUND OF THE INVENTION
Virus infection can lead to many diseases which are severely harmful to the health and life of the human being. Today, more than 3000 species of viruses over the whole world have been discovered and new types of viruses are being found. According to statistics, 60%-65% epidemic infectious diseases are caused by virus infection. Because of complexity of reciprocal action between viruses and hosts, most of antiviral agents, when exerting therapeutic action, have side-effects on the humanbeing or have lower antiviral function. This is the main reason why the antiviral drugs are developed so slowly. As for the types of existing antiviral drugs, the antiviral drugs now used in clinic are still very scarce and are far from meeting theneed of preventing and curing the virus diseases. It is important to investigate new antiviral drugs which have new antiviral mechanism, potent inhibitory activity and low toxicity.
5-hydroxyindole-3-carboxylate derivatives were originally studied as a new type of anti-influenza virus drug. The literatures, such as Grinev A. H., et al. Khim-Farm Zh, 1987, 21(1), 52; Parisheva E. K. et al. Khim Farm Zh, 1988, 22(5), 565;Mezentseva M. V. et al. Khim Farm Zh, 1990, 24(10), 52; Otova S. A., et al. Khim Farm Zh, 1992, 26(1), 52; Zotova S. A. et al. Khim Farm Zh, 1995, 29(1), 51, reported the synthesis of some 5-hydroxyindole-3-carboxylate derivatives and theirpharmacological activity. The experimental results show that some of them had anti-influenza virus activity and interferon-inducing and immunostimulative functions.
Ethyl 6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-(phenyl-thio- methyl)-1H-indole-3-carboxylate hydrochloride monohydrate (Arbidol, PCT Int Appl. WO 9008135(RUSS), 1990-6-26), one of 5-hydroxyindole-3-carboxylates, was launched inRussia Federation by VNIKhFI Co. Ltd. in 1993 for the prophylaxis and treatment of influenza A and B and acute respiratory viral infections.
In order to develop new type of highly effective antiviral drugs, the inventor has performed extensive studies on 5-hydroxy-indole-3-carboxylate derivatives. Modifications and changes are made on several structural sites and a new series of5-hydroxyindole-3-carboxylate derivatives are synthesized. Their antiviral activities are determined in vitro and the results showed that they had anti-influenza virus activity. Surprisingly, they are found to have potent anti-HBV and anti-HIVactivities. So the compounds are studied intensively and the invention is thereby completed.
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发表于 2011-10-23 23:46
