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1. 发明授权

US07888337B2 Synthesis of oseltamivir containing phosphonate congeners with anti-influenza activity 有权
标题翻译：含有具有抗流感活性的膦酸酯同系物的奥司他韦的合成
公开(公告)号：US07888337B2
公开(公告)日：2011-02-15
申请号：US12201955
申请日：2008-08-29
申请人： Chi-Huey Wong , Jim-Min Fang , Jiun-Jie Shie , Yih-Shyun Edmond Cheng , Jia-Tsrong Jan
发明人： Chi-Huey Wong , Jim-Min Fang , Jiun-Jie Shie , Yih-Shyun Edmond Cheng , Jia-Tsrong Jan
IPC分类号： A61K31/66
CPC分类号： A61K31/70 , A61K31/7076
摘要： Novel phosphonate compounds are described. The compounds have activity as neuraminidase inhibitors against wild-type and H274Y mutant of H1N1 and H5N1 viruses. The present disclosure also provides an enantioselective synthetic route to known neuraminidase inhibitors oseltamivir and the anti-flu drug Tamiflu®, as well as novel phosphonate compounds, via D-xylose. Another efficient and flexible synthesis of Tamiflu and the highly potent neuraminidase inhibitor Tamiphosphor was also achieved in 11 steps and >20% overall yields from the readily available fermentation product (1S-cis)-3-bromo-3,5 -cyclohexadiene-1,2-diol. Most of the reaction intermediates were obtained as crystals without tedious purification procedures. The key transformations include an initial regio- and stereoselective bromoamidation of a bromoarene cis-dihydrodiol, as well as the final palladium-catalyzed carbonylation and phosphonylation.
摘要翻译：描述了新的膦酸酯化合物。该化合物具有作为抗H1N1和H5N1病毒野生型和H274Y突变体的神经氨酸酶抑制剂的活性。本公开还提供了通过D-木糖对已知的神经氨酸酶抑制剂奥司他韦和抗流感药物Tamiflu以及新的膦酸酯化合物的对映选择性合成途径。 Tamiflu和高效神经氨酸酶抑制剂Tamiphosphor的另一种有效和灵活的合成还通过11个步骤实现，并且来自容易获得的发酵产物（1S-顺式）-3-溴-3,5-环己二烯-1的总收率> 20％ 2-二醇。大多数反应中间体是以晶体形式获得，而不需要繁琐的纯化程序。关键转化包括溴芳烃顺式 - 二氢二醇的初始区域和立体选择性溴酰胺化，以及最终的钯催化羰基化和膦酰化反应。

2. 发明申请

US20090149545A1 TREATMENT OF CORONAVIRUS INFECTION 失效
标题翻译：治疗冠状病毒感染
公开(公告)号：US20090149545A1
公开(公告)日：2009-06-11
申请号：US10856281
申请日：2004-05-28
申请人： Tsu-An Hsu , Hsing-Pang Hsieh , Yu-Sheng Chao , Chi-Min Chen , Jia-Tsrong Jan , Hwan-Wun Liu
发明人： Tsu-An Hsu , Hsing-Pang Hsieh , Yu-Sheng Chao , Chi-Min Chen , Jia-Tsrong Jan , Hwan-Wun Liu
IPC分类号： A61K31/166 , A61P31/12
CPC分类号： A61K31/33
摘要： A method for treating coronavirus infection by administering to a subject in need of the treatment an effective amount of one or more of the following compounds: aklavin, sanguinarine, amiodarone, chlorpromazine, clomiphene, dihydroergotamine, dipyridamole, emetine, ephedrine, prochlorperazine, promazine, propiomazine, aminacrine, fluphenazine, fenoterol, peruvoside, proglumide, atenolol, nerifolin, nefopam, cycloheximide, avermectin B1, bepridil, cinnarizine, ethisterone, pararosaniline, methylbenzethonium, niclosamide, pipobroman, homidium, calcimycin, anisomycin, metergoline, amodiaquine, danazol, danthron, ethopropazine, eucatropine, nortriptyline, resorcinol, mebhydrolin, mebeverine, trimipramine, triflupromazine, chlorprothixene, cyclobenzaprine, enoxacin, sulfanitran, monensin, nigericin, perphenazine, methoxamine, astemizole, trifluoperazine, acriflavinium, rotenone, acebutolol, quabain, methiothepin, convallatoxin, halcinonide, cyclosporin, pimethixene, mycophenolic acid, promethazine, mesoridazine, thioridazine, chlorprothixene, thiothixene, clozapine, haloperidol, haloperidol decanoate, loxapine, molindone, olanzapine, pimozide, quetiapine, risperidone, and amitriptyline.
摘要翻译：一种通过向需要治疗的受试者施用有效量的一种或多种以下化合物来治疗冠状病毒感染的方法：阿伐黄素，血根碱，胺碘酮，氯丙嗪，克罗米酚，二氢麦角胺，双嘧达莫，埃米汀，麻黄素，丙氯拉嗪，丙诺霉素，氨基吖啶，氟奋乃静，非诺替尔，紫苏碱，恩替洛尔，阿替洛尔，奈非泮，奈非泮，放线菌酮，阿维菌素B1，苯普利，桂酸，乙胺，对羟基苯胺，甲基苄索铵，氯硝柳胺，pipobroman，homidium，calcimycin，茴香霉素，metergoline，amodiaquine，达那唑，依托泊汀，间苯二酚，替康罗林，美勃司宁，间苯丙胺，三氟丙嗪，氯替噻吩，环苯扎林，依诺沙星，磺胺三苯胺，莫能菌素，尼日利亚，奋乃静，甲氧胺，阿司咪唑，三氟拉嗪，吖啶鎓，鱼藤酮，，环孢菌素，哌甲酯，霉酚酸，乙氮嗪，美索达嗪，硫利达嗪，氯普ix辛，硫代四氢噻吩，氯氮平，氟哌啶醇，氟哌啶醇癸酸酯，洛沙平，莫洛多内，奥氮平，匹莫齐特，喹硫平，利培酮和阿米替林。

3. 发明授权

US07544712B1 Treatment of coronavirus infection 失效
标题翻译：冠状病毒感染的治疗
公开(公告)号：US07544712B1
公开(公告)日：2009-06-09
申请号：US10856281
申请日：2004-05-28
申请人： Tsu-An Hsu , Hsing-Pang Hsieh , Yu-Sheng Chao , Chi-Min Chen , Jia-Tsrong Jan , Hwan-Wun Liu
发明人： Tsu-An Hsu , Hsing-Pang Hsieh , Yu-Sheng Chao , Chi-Min Chen , Jia-Tsrong Jan , Hwan-Wun Liu
IPC分类号： A61K31/33 , A01N47/10
CPC分类号： A61K31/33
摘要： A method for treating coronavirus infection by administering to a subject in need of the treatment an effective amount of one or more of the following compounds: aklavin, sanguinarine, amiodarone, chlorpromazine, clomiphene, dihydroergotamine, dipyridamole, emetine, ephedrine, prochlorperazine, promazine, propiomazine, aminacrine, fluphenazine, fenoterol, peruvoside, proglumide, atenolol, nerifolin, nefopam, cycloheximide, avermectin B1, bepridil, cinnarizine, ethisterone, pararosaniline, methylbenzethonium, niclosamide, pipobroman, homidium, calcimycin, anisomycin, metergoline, amodiaquine, danazol, danthron, ethopropazine, eucatropine, nortriptyline, resorcinol, mebhydrolin, mebeverine, trimipramine, triflupromazine, chlorprothixene, cyclobenzaprine, enoxacin, sulfanitran, monensin, nigericin, perphenazine, methoxamine, astemizole, trifluoperazine, acriflavinium, rotenone, acebutolol, quabain, methiothepin, convallatoxin, halcinonide, cyclosporin, pimethixene, mycophenolic acid, promethazine, mesoridazine, thioridazine, chlorprothixene, thiothixene, clozapine, haloperidol, haloperidol decanoate, loxapine, molindone, olanzapine, pimozide, quetiapine, risperidone, and amitriptyline.
摘要翻译：一种通过向需要治疗的受试者施用有效量的一种或多种以下化合物来治疗冠状病毒感染的方法：阿伐黄素，血根碱，胺碘酮，氯丙嗪，克罗米酚，二氢麦角胺，双嘧达莫，埃米汀，麻黄素，丙氯拉嗪，丙诺霉素，氨基吖啶，氟奋乃静，非诺替尔，紫苏碱，恩替洛尔，阿替洛尔，奈非泮，奈非泮，放线菌酮，阿维菌素B1，苯普利，桂酸，乙胺，对羟基苯胺，甲基苄索铵，氯硝柳胺，pipobroman，homidium，calcimycin，茴香霉素，metergoline，amodiaquine，达那唑，依托泊汀，间苯二酚，替康罗林，美勃司宁，间苯丙胺，三氟丙嗪，氯替噻吩，环苯扎林，依诺沙星，磺胺三苯胺，莫能菌素，尼日利亚，奋乃静，甲氧胺，阿司咪唑，三氟拉嗪，吖啶鎓，鱼藤酮，，环孢菌素，哌甲酯，霉酚酸，乙氮嗪，美索达嗪，硫利达嗪，氯普ix辛，硫代四氢噻吩，氯氮平，氟哌啶醇，氟哌啶醇癸酸酯，洛沙平，莫洛多内，奥氮平，匹莫齐特，喹硫平，利培酮和阿米替林。

4. 发明申请

US20080214442A1 Anti-Viral Effect of an Extract of Ganoderma Lucidum 审中-公开
标题翻译：灵芝提取物的抗病毒作用
公开(公告)号：US20080214442A1
公开(公告)日：2008-09-04
申请号：US11859729
申请日：2007-09-21
申请人： Alice Yu , Chi-Huey Wong , Jia Tsrong Jan , Y.-S. Edmond Cheng
发明人： Alice Yu , Chi-Huey Wong , Jia Tsrong Jan , Y.-S. Edmond Cheng
IPC分类号： A61K38/16 , C07K14/00 , A61P31/12
CPC分类号： C07K2/00 , A61K36/074 , A61K38/00
摘要： Compositions and methods for the treatment viral infections in organisms, particularly flu virus. The methods and compositions of the disclosure involve the administration to mammals and immune cells of a fucose-containing glycoprotein fraction from Reishi. An extract of G. lucidum induces immune responses that are shown to induce increase survivability in mice injected with lethal does of influenza virus. The effect is increased when the G. lucidum extract is dosed prior to injection of the lethal dose of influenza virus.
摘要翻译：用于治疗生物体中的病毒感染的组合物和方法，特别是流感病毒。本公开的方法和组合物涉及向来自Reishi的含岩藻糖的糖蛋白部分的哺乳动物和免疫细胞施用。灵芝的提取物诱导免疫应答，显示其在注射致死性流感病毒的小鼠中诱导增加的存活能力。当在注射致死剂量的流感病毒之前配制灵芝提取物时，效果增加。

5. 发明授权

US08481571B2 Anti-coronavirus compounds 有权
标题翻译：抗冠状病毒化合物
公开(公告)号：US08481571B2
公开(公告)日：2013-07-09
申请号：US11121314
申请日：2005-05-03
申请人： Chi-Huey Wong , Chung-Yi Wu , Jia-Tsrong Jan
发明人： Chi-Huey Wong , Chung-Yi Wu , Jia-Tsrong Jan
IPC分类号： A61K31/44 , A61K31/40 , A61K31/165 , A61K31/325
CPC分类号： A61K31/165 , A61K31/325 , A61K31/40 , A61K31/44
摘要： A method of treating coronavirus infection. The method includes administering to a subject suffering from or being at risk of suffering from such infection an effective amount of a compound of formula (I). Each variable in this formula is defined in the specification.
摘要翻译：治疗冠状病毒感染的方法。该方法包括给患有或有风险患有此类感染的受试者施用有效量的式（I）化合物。该公式中的每个变量在规范中定义。

6. 发明申请

US20100113397A1 SYNTHESIS OF OSELTAMIVIR CONTAINING PHOSPHONATE CONGENERS WITH ANTI-INFLUENZA ACTIVITY 有权
标题翻译：含有抗感染活性的含有磷酸肌酸钠的奥沙利铂的合成
公开(公告)号：US20100113397A1
公开(公告)日：2010-05-06
申请号：US12201955
申请日：2008-08-29
申请人： Chi-Huey Wong , Jim-Min Fang , Jiun-Jie Shie , Yih-Shyun Edmond Cheng , Jia-Tsrong Jan
发明人： Chi-Huey Wong , Jim-Min Fang , Jiun-Jie Shie , Yih-Shyun Edmond Cheng , Jia-Tsrong Jan
IPC分类号： A61K31/66 , A61P31/16 , C07F9/02
CPC分类号： A61K31/70 , A61K31/7076
摘要： Novel phosphonate compounds are described. The compounds have activity as neuraminidase inhibitors against wild-type and H274Y mutant of H1N1 and H5N1 viruses. The present disclosure also provides an enantioselective synthetic route to known neuraminidase inhibitors oseltamivir and the anti-flu drug Tamiflu®, as well as novel phosphonate compounds, via D-xylose. Another efficient and flexible synthesis of Tamiflu and the highly potent neuraminidase inhibitor Tamiphosphor was also achieved in 11 steps and >20% overall yields from the readily available fermentation product (1S-cis)-3-bromo-3,5-cyclohexadiene-1,2-diol. Most of the reaction intermediates were obtained as crystals without tedious purification procedures. The key transformations include an initial regio- and stereoselective bromoamidation of a bromoarene cis-dihydrodiol, as well as the final palladium-catalyzed carbonylation and phosphonylation.
摘要翻译：描述了新的膦酸酯化合物。该化合物具有作为抗H1N1和H5N1病毒野生型和H274Y突变体的神经氨酸酶抑制剂的活性。本公开还提供了通过D-木糖对已知的神经氨酸酶抑制剂奥司他韦和抗流感药物Tamiflu以及新的膦酸酯化合物的对映选择性合成途径。 Tamiflu和高效神经氨酸酶抑制剂Tamiphosphor的另一种有效和灵活的合成还通过11个步骤实现，并且来自容易获得的发酵产物（1S-顺式）-3-溴-3,5-环己二烯-1的总收率> 20％ 2-二醇。大多数反应中间体是以晶体形式获得，而不需要繁琐的纯化程序。关键转化包括溴芳烃顺式 - 二氢二醇的初始区域和立体选择性溴酰胺化，以及最终的钯催化羰基化和膦酰化反应。

7. 发明申请

US20060160866A1 Anti-coronavirus compounds 有权
公开(公告)号：US20060160866A1
公开(公告)日：2006-07-20
申请号：US11121314
申请日：2005-05-03
申请人： Chi-Huey Wong , Chung-Yi Wu , Jia-Tsrong Jan
发明人： Chi-Huey Wong , Chung-Yi Wu , Jia-Tsrong Jan
IPC分类号： A61K31/44 , A61K31/40 , A61K31/325 , A61K31/165
CPC分类号： A61K31/165 , A61K31/325 , A61K31/40 , A61K31/44
摘要： A method of treating coronavirus infection. The method includes administering to a subject suffering from or being at risk of suffering from such infection an effective amount of a compound of formula (I). Each variable in this formula is defined in the specification.

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