公开(公告)号：US06677350B1

公开(公告)日：2004-01-13

申请号：US09667131

申请日：2000-09-21

申请人： Yuh-Meei Lin

发明人： Yuh-Meei Lin

IPC分类号： A61K3144

CPC分类号： A61K31/352 ,  A61K31/12

摘要： The present invention relates to compounds, compositions and methods for the prevention or treatment of mycobacterium infections. The compounds are naturally occurring and synthetic biflavonoids, flavonoids, chalcones and chalcone like compounds. The compounds were screened for anti-mycobacterium activity. Of the compounds showing anti-mycobacterium activity, eight were identified as particularly potent, exhibiting greater than 90% inhibition of the growth of Mtb at a concentration of 12.5 &mgr;g/mL. The actual minimum inhibitory concentrations (MIC), defined as the lowest concentration inhibiting 99% of the inoculum, for the preferred compounds ranged from 6.8 to 48.3 &mgr;M.

摘要翻译： 本发明涉及用于预防或治疗分枝杆菌感染的化合物，组合物和方法。 这些化合物是天然存在的和合成的双黄酮，类黄酮，查尔酮和查尔酮类化合物。 筛选化合物的抗分枝杆菌活性。 在显示抗分枝杆菌活性的化合物中，8种被鉴定为特别有效的，在12.5μg/ mL浓度下表现出大于90％的Mtb生长抑制。 对于优选的化合物，实际的最小抑制浓度（MIC）定义为抑制99％接种物的最低浓度范围为6.8至48.3μM。

公开(公告)号：US06399654B1

公开(公告)日：2002-06-04

申请号：US09060839

申请日：1998-04-15

申请人： Yuh-Meei Lin ,  David E. Zembower ,  Michael T. Flavin ,  Ralph Schure ,  Geng-Xian Zhao

发明人： Yuh-Meei Lin ,  David E. Zembower ,  Michael T. Flavin ,  Ralph Schure ,  Geng-Xian Zhao

IPC分类号： A61K3135

CPC分类号： A61K38/19 ,  A61K31/35 ,  A61K31/352 ,  A61K31/47 ,  A61K31/55 ,  A61K31/70 ,  A61K31/7048 ,  A61K38/212 ,  A61K45/06 ,  C07D311/30 ,  C07D311/32 ,  A61K38/20 ,  A61K2300/00

摘要： Substantially purified antiviral biflavanoids robustaflavone, hinokiflavone, amentoflavone, agathisflavone, volkensiflavone, morelloflavone, rhusflavanone, succedaneaflavanone, GB-1a, and GB-2a are provided. Antiviral biflavanoid derivatives and salt forms thereof, e.g., robustaflavone tetrasulfate potassium salt, and methods for preparing the same are also disclosed. Pharmaceutical compositions which include the antiviral biflavanoids, derivatives or salts thereof are also provided alone or in combination with at least one antiviral agent such as 3TC. Also disclosed is an improved method for obtaining substantially pure robustaflavone from plant material. The biflavanoid compounds, derivatives or salts thereof of the invention may be used in a method for treating and/or preventing viral infections caused by viral agents such as influenza, e.g., influenza A and B; hepatitis, e.g., hepatitis B; human immunodeficiency virus, e.g., HIV-1; Herpes viruses (HSV-1 and HSV-2); Varicella Zoster virus (VZV); and measles. For instance, semi-synthetic hexa-O-acetate and hexa-O-methyl ether derivatives of robustaflavone have been found to be effective in a method for treating or preventing hepatitis B viral infections. Compositions which include these robustaflavone derivatives along with methods for preparing and using the same are also provided. These compositions may be used alone or in combination with at least one antiviral agent such as 3TC.

摘要翻译： 提供了大量纯化的抗病毒双歧杆菌强壮黄酮，桧醇酮，黄酮黄酮，恶灵素，伏安芬酮，多氟黄酮，黄豆酮，琥珀醛缩酮，GB-1a和GB-2a。 还公开了抗病毒双变异构物衍生物及其盐形式，例如耐久性黄酮四硫酸钾钾盐及其制备方法。 包括抗病毒双弗来菌素，其衍生物或盐的药物组合物也单独提供或与至少一种抗病毒剂如3TC组合提供。 还公开了一种用于从植物材料获得基本上纯的健壮的黄豆黄酮的改进方法。 本发明的双叉子化合物，其衍生物或盐可用于治疗和/或预防由病毒药物如流感引起的病毒感染的方法，例如流感A和B; 肝炎，例如乙型肝炎; 人类免疫缺陷病毒，例如HIV-1; 疱疹病毒（HSV-1和HSV-2）; 水痘带状疱疹病毒（VZV）; 和麻疹。 例如，已经发现健康黄酮的半合成六-O-乙酸酯和六-O-甲基醚衍生物在治疗或预防乙型肝炎病毒感染的方法中是有效的。 还提供了包括这些耐久性黄酮衍生物的组合物以及其制备和使用方法。 这些组合物可以单独使用或与至少一种抗病毒剂如3TC组合使用。

公开(公告)号：US06225481B1

公开(公告)日：2001-05-01

申请号：US09137767

申请日：1998-08-21

申请人： David E. Zembower ,  Heping Zhang ,  Michael T. Flavin ,  Yuh-Meei Lin

发明人： David E. Zembower ,  Heping Zhang ,  Michael T. Flavin ,  Yuh-Meei Lin

IPC分类号： C07D31176

CPC分类号： C07F5/025 ,  C07D311/30 ,  C07F7/2208

摘要： Robustaflavone, intermediates and analogues thereof and a method for synthesizing the same are provided. The method involves constructing apigenin ethers containing functionalities at the 6- and 3′-positions which could be cross-coupled using transition metal catalysis. The method also involves development of a regioselective iodination of an apigenin derivative at the 6-position, formation of an apigenin 3′-boronate using a palladium-catalyzed exchange of the corresponding 3′-iodide with a diboron reagent. Finally, Suzuki coupling to form the sterically congested 6-3′″ biaryl bond of robustaflavone provides access to the desired biflavanoid system. Robustaflavone intermediates and analogues may be used to prepare analogues of other biflavanoids such as hinokifavone, rhusflavone and succedaneaflavone.

摘要翻译： 提供了罗曲斯黄酮，其中间体及其类似物及其合成方法。 该方法涉及在6-和3'-位上构建含有功能性的芹菜素醚，其可以使用过渡金属催化交联。 该方法还涉及在6位开发区域选择性碘化芹菜素衍生物，使用相应的3'-碘化物与二硼试剂的钯催化交换形成芹菜素3'-硼酸酯。 最后，Suzuki偶联形成强壮的黄酮的空间拥塞的6-3“联芳基键提供了所需的双类体系。 罗非糖黄酮中间体和类似物可用于制备其他双紫杉醇的类似物，例如依诺呋酮，香豆素和琥珀酰黄酮。

公开(公告)号：US5948918A

公开(公告)日：1999-09-07

申请号：US59913

申请日：1998-04-14

申请人： Yuh-Meei Lin ,  Michael T. Flavin ,  Ralph Schure ,  David E. Zembower ,  Gen-Xian Zhao

发明人： Yuh-Meei Lin ,  Michael T. Flavin ,  Ralph Schure ,  David E. Zembower ,  Gen-Xian Zhao

IPC分类号： A61K31/35 ,  A61K31/352 ,  A61P31/12 ,  A61P31/22 ,  C07D311/30 ,  C07D311/32 ,  C07D407/10

CPC分类号： A61K31/7048 ,  A61K31/352 ,  C07D311/30 ,  C07D311/32

摘要： Substantially purified antiviral biflavanoids robustaflavone, hinokiflavone, amentoflavone, agathisflavone, volkensiflavone, morelloflavone, rhusflavanone, succedaneaflavanone, GB-1a, and GB-2a are provided. Antiviral biflavanoid derivatives and salt forms thereof, e.g., robustaflavone tetrasulfate potassium salt, and methods for preparing the same are also disclosed. Pharmaceutical compositions which include the antiviral biflavanoids, derivatives or salts thereof are also provided. Also disclosed is an improved method for obtaining substantially pure robustaflavone from plant material. The biflavanoid compounds, derivatives or salts thereof of the invention may be used in a method for treating and/or preventing viral infections caused by viral agents such as influenza, e.g., influenza A and B; hepatitis, e.g., hepatitis B; human immunodeficiency virus, e.g., HIV-1; Herpes viruses (HSV-1 and HSV-2); Varicella Zoster virus (VZV); and measles.

摘要翻译： 提供了大量纯化的抗病毒双歧杆菌强壮黄酮，桧醇酮，黄酮黄酮，恶灵素，伏安芬酮，多氟黄酮，黄豆酮，琥珀醛缩酮，GB-1a和GB-2a。 还公开了抗病毒双变异构物衍生物及其盐形式，例如耐久性黄酮四硫酸钾钾盐及其制备方法。 还提供了包括抗病毒双变种类，其衍生物或盐的药物组合物。 还公开了一种用于从植物材料获得基本上纯的健壮的黄豆黄酮的改进方法。 本发明的双叉子化合物，其衍生物或盐可用于治疗和/或预防由病毒药物如流感引起的病毒感染的方法，例如流感A和B; 肝炎，例如乙型肝炎; 人类免疫缺陷病毒，例如HIV-1; 疱疹病毒（HSV-1和HSV-2）; 水痘带状疱疹病毒（VZV）; 和麻疹。

公开(公告)号：US6160131A

公开(公告)日：2000-12-12

申请号：US213192

申请日：1998-12-17

申请人： Yuh-Meei Lin ,  Herbert M. Anderson ,  Tuah R. Jenta ,  Michael J. Williams ,  Michael T. Flavin ,  Ze-Qi Xu

发明人： Yuh-Meei Lin ,  Herbert M. Anderson ,  Tuah R. Jenta ,  Michael J. Williams ,  Michael T. Flavin ,  Ze-Qi Xu

IPC分类号： C07D493/14 ,  C07D311/78 ,  C07D407/14

CPC分类号： C07D493/14

摘要： An efficient and scalable method is reported for the isolation of costatolide (2), an HIV-1-specific nonnucleoside reverse transcriptase inhibitor (NNRTI), from the latex of Calophyllum plants such as C. teysmannii var. inophylloide. An overall yield of 10.6% of costatolide, with a purity of 96%, was obtained by repetitive recrystallization of the latex from a single organic solvent after the oily material was removed by treatment with hexane. A second major component of the latex, soulattrolide (3), another HIV-1 NNRTI, was also isolated. Both compounds were characterized by spectroscopic and chromatographic analyses and their in vitro anti-HIV activities were also confirmed. The results suggest that sufficient supplies of costatolide can be obtained in a relatively low-cost manner from natural sources.

摘要翻译： 报道了从Calphyllum植物如C.teysmannii变种的胶乳中分离Costatolide（2）（一种HIV-1特异性非核苷逆转录酶抑制剂（NNRTI））的有效和可扩展的方法。 叶黄素 通过用己烷处理除去油状物后，通过从单一有机溶剂中的胶乳的重复重结晶，可以获得纯度为96％的花色滑石的总产率10.6％。 还分离了乳胶的另一个主要组分，即另外的HIV-1 NNRTI的soulattrolide（3）。 通过光谱和色谱分析表征了两种化合物，并证实了其体外抗HIV活性。 结果表明，可以以相对低成本的方式从天然来源获得足够的costatolide供应。

公开(公告)号：US06268393B1

公开(公告)日：2001-07-31

申请号：US09417672

申请日：1999-10-14

申请人： Ze-Qi Xu ,  Yuh Meei Lin ,  Michael T. Flavin

发明人： Ze-Qi Xu ,  Yuh Meei Lin ,  Michael T. Flavin

IPC分类号： A61K31353

CPC分类号： A61K45/06 ,  A61K31/366 ,  A61K31/37

摘要： Calanolides and analogues thereof that demonstrate potent mycobacterium activity are provided. Also provided is a method of using calanolides and analogues thereof for treating or preventing mycobacterium infections. The calanolides and analogues thereof provided are obtained via syntheses employing chromene 4 and chromanone 7 as key intermediates.

摘要翻译： 提供了表现出有效的分枝杆菌活性的卡立仑内酯及其类似物。 还提供了用于治疗或预防分枝杆菌感染的calanolide及其类似物的方法。 所提供的癸内酰胺及其类似物通过使用色烯4和苯并二氢吡喃酮7作为关键中间体的合成获得。

公开(公告)号：US5773462A

公开(公告)日：1998-06-30

申请号：US668284

申请日：1996-06-21

申请人： Yuh-Meei Lin ,  Michael T. Flavin ,  Ralph Schure ,  David E. Zembower ,  Gen-Xian Zhao

发明人： Yuh-Meei Lin ,  Michael T. Flavin ,  Ralph Schure ,  David E. Zembower ,  Gen-Xian Zhao

IPC分类号： A61K31/35 ,  A61K31/352 ,  A61P31/12 ,  A61P31/22 ,  C07D311/30 ,  C07D311/32 ,  C07D407/10

CPC分类号： A61K31/7048 ,  A61K31/352 ,  C07D311/30 ,  C07D311/32

摘要： Substantially purified antiviral biflavanoids robustaflavone, hinokiflavone, amentoflavone, agathisflavone, volkensiflavone, morelloflavone, rhusflavanone, succedaneaflavanone, GB-1a, and GB-2a are provided. Antiviral biflavanoid derivatives and salt forms thereof, e.g., robustaflavone tetrasulfate potassium salt, and methods for preparing the same are also disclosed. Pharmaceutical compositions which include the antiviral biflavanoids, derivatives or salts thereof are also provided. Also disclosed is an improved method for obtaining substantially pure robustaflavone from plant material. The biflavanoid compounds, derivatives or salts thereof of the invention may be used in a method for treating and/or preventing viral infections caused by viral agents such as influenza, e.g., influenza A and B; hepatitis, e.g., hepatitis B; human immunodeficiency virus, e.g., HIV-1; Herpes viruses (HSV-1 and HSV-2); Varicella Zoster virus (VZV); and measles.