公开(公告)号：US06255317B1

公开(公告)日：2001-07-03

申请号：US09233325

申请日：1999-01-20

申请人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

发明人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

IPC分类号： C07D48704

CPC分类号： C07D471/04 ,  C07D491/04

摘要： The present invention provides a cholesterol biosynthesis inhibitor which specifically inhibits the sterol 14-reductase which is involved in the distal pathway of cholesterol biosynthesis, a compound of formula (1) below and the use of an extract or the compound of formula (1) for treating hypercholesterolaemia or hyperlipidaemia. The inhibitor comprises an extract obtained by extracting Corydalis Turtschaninowii Besser with a solvent, or an organic layers obtained by partitioning an extract from Corydalis Turtschaninowii Besser with an organic solvent. The extract contains 7,8,13,13&agr;-tetrahydrocoridaline or its derivative, as the active ingredients, which specifically inhibits the enzyme which is involved in the distal pathway of the cholesterol biosynthesis. R1 and R2 which may be the same or different from each other, represent a hydroxy group or an alkoxy group having 1 to 4 carbon atoms or both of R1 and R2 represent a methylenedioxy group; R3 represents a hydrogen atom; R4 and R5 which may be the same or different from each other, represent a hydroxy group, a hydroxyethylamino group or an alkoxy group having 1 to 4 carbon atoms; R6 represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 3 to 8 carbon atoms, a cycloalkylalkyl group having 1 to 7 carbon atoms, a holoalkyl group having 1 to 4 carbon atoms, an ethoxycarbonyl group, an ethoxycarbonylmethyl group, a hydroxycarbonylmethyl group, 1-ethoxycarbonylethyl group, or 2-valerolactonyl group; and z represents a halogen atom.

摘要翻译： 本发明提供一种胆固醇生物合成抑制剂，其特异性抑制参与胆固醇生物合成的远端途径的甾醇14-还原酶，下式（1）的化合物和提取物或式（1）化合物用于 治疗高胆固醇血症或高脂血症。 抑制剂包括通过用溶剂提取紫茎泽兰植物提取物获得的提取物或通过用有机溶剂分离来自紫堇（Corydalis Turtschaninowii Besser）的提取物获得的有机层。 提取物含有7,8,13,13α-四氢花青苷或其衍生物作为活性成分，其特异性抑制参与胆固醇生物合成的远端途径的酶.R1和R2可以相同或不同 另一个表示羟基或具有1至4个碳原子的烷氧基，或者R 1和R 2都表示亚甲二氧基; R 3表示氢原子; R 4和R 5可以相同或不同，表示羟基 基团，羟乙基氨基或具有1〜4个碳原子的烷氧基; R6表示氢原子，碳原子数1〜8的烷基，碳原子数3〜8的烯基，碳原子数为1〜7的环烷基烷基 原子，具有1至4个碳原子的全烷基，乙氧基羰基，乙氧基羰基甲基，羟基羰基甲基，1-乙氧基羰基乙基或2-戊内酰基; 和z表示卤素原子。

公开(公告)号：US6030979A

公开(公告)日：2000-02-29

申请号：US235489

申请日：1999-01-22

申请人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

发明人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

IPC分类号： C07D455/03 ,  A61K31/00 ,  A61K31/435 ,  A61K31/4353 ,  A61K31/4375 ,  A61K31/47 ,  A61P3/00 ,  A61P3/06 ,  A61P43/00 ,  C07D471/04 ,  C07D491/056 ,  C07D491/147 ,  A61K31/44

CPC分类号： C07D471/04 ,  Y10S514/824

摘要： The present invention provides a pharmaceutical composition comprising 5,6-dihydrodibenzo[a,g]quinolizinium derivative and the salts thereof of formula (I) which specifically inhibits the sterol 14-reductase which is involved in the distal pathway of cholesterol biosynthesis, and the use of the compound of formula (I) for treating hypercholesterolaemia or hyperlipidaemia. ##STR1##

摘要翻译： 本发明提供一种包含5,6-二氢二苯并[a，g]喹啉鎓衍生物及其特异性抑制参与胆固醇生物合成的远端途径的甾醇14-还原酶的式（I）的盐的药物组合物， 使用式（I）化合物治疗高胆固醇血症或高脂血症。

公开(公告)号：US6028197A

公开(公告)日：2000-02-22

申请号：US235482

申请日：1999-01-22

申请人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

发明人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

IPC分类号： C07D455/03 ,  A61K31/00 ,  A61K31/435 ,  A61K31/4353 ,  A61K31/4375 ,  A61K31/47 ,  A61P3/00 ,  A61P3/06 ,  A61P43/00 ,  C07D471/04 ,  C07D491/056 ,  C07D491/147 ,  C07D215/20

CPC分类号： C07D471/04 ,  Y10S514/824

摘要： The present invention provides a 5,6-dihydrodibenzo[a,g]quinolizinium derivative and the salts thereof of formula (I) which specifically inhibits the sterol 14-reductase which is involved in the distal pathway of cholesterol biosynthesis, and the use of the compound of formula (I) for treating hypercholesterolaemia or hyperlipidaemia. ##STR1## wherein, R.sup.1 and R.sup.2 which may be the same or different from each other, represent a hydroxy group or an alkoxy group having 1 to 4 carbons or R.sup.1 and R.sup.2 together represent a methylenedioxy group;R.sup.3 represents a hydroxy group or an alkoxy group having 1 to 4 carbons;R.sup.4 represents a hydrogen atom, an alkyl group having 1 to 8 carbons, or an alkenyl group having 3 to 8 carbons;X represents inorganic acid ion, organic acid ion or halide, more particularly, nitrate, sulfate, acetate, tartrate, maleate, succinate, citrate, fumarate, aspartate, salicylate, glycerate, ascorbate, fluoride, chloride, iodide or bromide,Z represents an alkyl group having 5 to 12 carbons, or an alkenyl group having 4 to 6 carbons, a N-benzotriazolyl group, a quinolinyl group, a furyl group, a substituted furyl group, or a radical represented by the formula ##STR2## wherein Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4 and Z.sup.5 which may be the same or different from each other, represent a hydrogen atom, halogen, an alkyl group having 1 to 5 carbons, a trifluoromethyl group, a phenyl group, a substituted phenyl group, a nitro group, an alkoxy group having 1 to 4 carbons, a methylenedioxy group, a trifluoromethoxy group, a hydroxy group, a benzyloxy group, a phenoxy group, a vinyl group, a benzenesulfonylmethyl group or a methoxycarbonyl group; andA and B which may be the same or different from each other, represent carbon or nitrogen.

摘要翻译： 本发明提供特异性抑制参与胆固醇生物合成的远端途径的甾醇14-还原酶的式（I）的5,6-二氢二苯并[a，g]喹啉鎓衍生物及其盐， 用于治疗高胆固醇血症或高脂血症的式（I）化合物。 其中，可以相同或不同的R 1和R 2表示羟基或具有1至4个碳的烷氧基，或者R 1和R 2一起表示亚甲二氧基; R3表示羟基或碳原子数1〜4的烷氧基， R4表示氢原子，碳原子数1〜8的烷基或碳原子数3〜8的烯基， X表示无机酸离子，有机酸离子或卤化物，更特别是硝酸盐，硫酸盐，乙酸盐，酒石酸盐，马来酸盐，琥珀酸盐，柠檬酸盐，富马酸盐，天冬氨酸盐，水杨酸盐，甘油酸盐，抗坏血酸盐，氟化物，氯化物，碘化物或溴化物，Z表示 碳数为5〜12的烷基或碳原子数为4〜6的烯基，N-苯并三唑基，喹啉基，呋喃基，取代呋喃基，或下式所示的基团其中Z1，Z2，Z3 ，Z4和Z5可以相同或不同，表示氢原子，卤素，碳原子数为1〜5的烷基，三氟甲基，苯基，取代苯基，硝基，烷氧基 具有1至4个碳的基团，亚甲二氧基，三氟甲氧基，羟基，苄氧基，苯氧基，乙烯基，苯磺酰基甲基或甲氧基羰基; 可以相同或不同的A和B表示碳或氮。

公开(公告)号：US6008356A

公开(公告)日：1999-12-28

申请号：US208877

申请日：1998-12-10

申请人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

发明人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

IPC分类号： A61K31/00 ,  A61K31/435 ,  A61K31/4353 ,  A61K31/4375 ,  A61K31/47 ,  A61K36/71 ,  A61P31/00 ,  A61P31/10 ,  C07D455/03 ,  C07D471/04 ,  C07D491/056 ,  C07D221/18

CPC分类号： C07D455/00 ,  C07D471/04

摘要： The novel compounds of the following chemical formulae (I) and (II) exhibit in vitro antifungal activity against fungi including cutaneous filamentous fungus, such as Epidermophyton, Microsporum, Trichophyton, Sporothrix schenckii, Aspergillus or Candida. The compounds of the present invention exhibit in vitro antifungal activity at the concentration of 1-100 .mu.g/ml. ##STR1## wherein R.sup.1, R.sup.2, and R.sup.4 may be the same or different, and represent C.sub.1 -C.sub.5 alkoxy, R.sup.3 represents hydrogen or C.sub.1 -C.sub.10 alkyl, A.sup.- represents inorganic acid ion, organic acid ion or halide, R.sup.5 represents hydrogen, pyridylmethyl, substituted pyridylmethyl or a group having the following chemical formula(XI) ##STR2## wherein Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4 and Z.sup.5 may be the same or different and represent hydrogen, halogen, C.sub.1 -C.sub.5 alkyl, trifluoromethyl, phenyl, substituted phenyl, nitro, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylamino, acetylamino, C.sub.1 -C.sub.8 trialkyl ammonium, guanidinyl, methylthio, ethylthio, trifluoromethoxy, hydroxy, phenoxy, vinyl, carboxyl and C.sub.1 -C.sub.2 alkoxycarbonyl group.

摘要翻译： 以下化学式（I）和（II）的新化合物表现出对真皮的体外抗真菌活性，包括皮肤丝状真菌，如表皮癣菌，微孢子虫，毛癣菌，阵孢曲霉，曲霉或假丝酵母。 本发明的化合物以1-100μg/ ml的浓度显示体外抗真菌活性。 其中R1，R2和R4可以相同或不同，表示C1-C5烷氧基，R3表示氢或C1-C10烷基，A-表示无机酸离子，有机酸离子或卤化物，R5表示氢，吡啶基甲基，取代 吡啶基甲基或具有以下化学式（XI）的基团，其中Z 1，Z 2，Z 3，Z 4和Z 5可以相同或不同，表示氢，卤素，C 1 -C 5烷基，三氟甲基，苯基，取代的苯基，硝基， C4烷氧基，C1-C4烷基氨基，乙酰氨基，C1-C8三烷基铵，胍基，甲硫基，乙硫基，三氟甲氧基，羟基，苯氧基，乙烯基，羧基和C1-C2烷氧基羰基。

公开(公告)号：US06239139B1

公开(公告)日：2001-05-29

申请号：US09233323

申请日：1999-01-20

申请人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

发明人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

IPC分类号： C07D491056

CPC分类号： C07D471/04 ,  C07D491/04

摘要： The present invention provides a cholesterol biosynthesis inhibitor which specifically inhibits the sterol 14-reductase which is involved in the distal pathway of cholesterol biosynthesis, a compound of formula (1) below and the use of an extract or the compound of formula (1) for treating hypercholesterolaemia or hyperlipidaemia. The inhibitor comprises an extract obtained by extracting Corydalis Turtschaninowii Besser with a solvent, or an organic layers obtained by partitioning an extract from Corydalis Turtschaninowii Besser with an organic solvent. The extract contains 7,8,13,13&agr;-tetrahydrocoridaline or its derivative, as the active ingredients, which specifically inhibits the enzyme which is involved in the distal pathway of the cholesterol biosynthesis. R1 and R2 which may be the same or different from each other, represent a hydroxy group or an alkoxy group having 1 to 4 carbon atoms or both of R1 and R2 represent a methylenedioxy group; R3 represents a hydrogen atom; R4 and R5 which may be the same or different from each other, represent a hydroxy group, a hydroxyethylamino group or an alkoxy group having 1 to 4 carbon atoms; R6 represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 3 to 8 carbon atoms, a cycloalkylalkyl group having 1 to 7 carbon atoms, a holoalkyl group having 1 to 4 carbon atoms, an ethoxycarbonyl group, an ethoxycarbonylmethyl group, a hydroxycarbonylmethyl group, 1-ethoxycarbonylethyl group, or 2-valerolactonyl group.

摘要翻译： 本发明提供了一种胆固醇生物合成抑制剂，其特异性抑制参与胆固醇生物合成的远端途径的甾醇14-还原酶，以下式（1）的化合物以及提取物或式（1）化合物用于 治疗高胆固醇血症或高脂血症。 抑制剂包括通过用溶剂提取紫茎泽兰植物提取物获得的提取物或通过用有机溶剂分离来自紫堇（Corydalis Turtschaninowii Besser）的提取物获得的有机层。 提取物含有7,8,13,13α-四氢花青苷或其衍生物作为活性成分，其特异性抑制参与胆固醇生物合成的远端途径的酶.R1和R2可以相同或不同 另一个表示羟基或具有1至4个碳原子的烷氧基，或者R 1和R 2都表示亚甲二氧基; R 3表示氢原子; R 4和R 5可以相同或不同，表示羟基 基团，羟乙基氨基或具有1〜4个碳原子的烷氧基; R6表示氢原子，碳原子数1〜8的烷基，碳原子数3〜8的烯基，碳原子数为1〜7的环烷基烷基 原子，具有1至4个碳原子的全烷基，乙氧基羰基，乙氧基羰基甲基，羟基羰基甲基，1-乙氧基羰基乙基或2-戊内酰基。

公开(公告)号：US6030978A

公开(公告)日：2000-02-29

申请号：US208641

申请日：1998-12-10

申请人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

发明人： Jung Ho Kim ,  Tae Neung Jhong ,  Young Ki Paik ,  Joon Seo Park ,  Eui Deok Kim ,  You Suk Lee ,  Seung Un Kim

IPC分类号： A61K31/00 ,  A61K31/435 ,  A61K31/4353 ,  A61K31/4375 ,  A61K31/47 ,  A61K36/71 ,  A61P31/00 ,  A61P31/10 ,  C07D455/03 ,  C07D471/04 ,  C07D491/056 ,  A61K31/44

CPC分类号： C07D455/00 ,  C07D471/04

摘要： The antifungal formulation comprising the novel compounds of the following chemical formulae (I) and (II) exhibit in vitro antifungal activity against fungi including cutaneous filamentous fungus, such as Epidermophyton, Microsporum, Trichophyton, Sporothrix schenckii, Aspergillus or Candida. The formulation of the present invention exhibit in vitro antifungal activity at the concentration of 1-100 .mu.g/ml. ##STR1## wherein R.sup.1, R.sup.2, and R.sup.4 may be the same or different, and represent C.sub.1 -C.sub.5 alkoxy, R.sup.3 represents hydrogen or C.sub.1 -C.sub.10 alkyl, A.sup.- represents inorganic acid ion, organic acid ion or halide, R.sup.5 represents hydrogen, pyridylmethyl, substituted pyridylmethyl or a group having the following chemical formula(XI) ##STR2## wherein Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4 and Z.sup.5 may be the same or different and represent hydrogen, halogen, C.sub.1 -C.sub.5 alkyl, trifluoromethyl, phenyl, substituted phenyl, nitro, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylamino, acetylamino, C.sub.1 -C.sub.8 trialkyl ammonium, guanidinyl, methylthio, ethylthio, trifluoromethoxy, hydroxy, phenoxy, vinyl, carboxyl and C.sub.1 -C.sub.2 alkoxycarbonyl group.

摘要翻译： 包含以下化学式（I）和（II）的新化合物的抗真菌制剂表现出对真菌的体外抗真菌活性，包括皮肤丝状真菌，例如表皮癣菌，微孢子虫，毛癣菌，斯曲霉，曲霉或假丝酵母。 本发明的制剂以1-100μg/ ml的浓度显示体外抗真菌活性。 其中R1，R2和R4可以相同或不同，表示C1-C5烷氧基，R3表示氢或C1-C10烷基，A-表示无机酸离子，有机酸离子或卤化物，R5表示氢，吡啶基甲基，取代 吡啶基甲基或具有以下化学式（XI）的基团，其中Z 1，Z 2，Z 3，Z 4和Z 5可以相同或不同，表示氢，卤素，C 1 -C 5烷基，三氟甲基，苯基，取代的苯基，硝基， C4烷氧基，C1-C4烷基氨基，乙酰氨基，C1-C8三烷基铵，胍基，甲硫基，乙硫基，三氟甲氧基，羟基，苯氧基，乙烯基，羧基和C1-C2烷氧基羰基。