公开(公告)号：US4156728A

公开(公告)日：1979-05-29

申请号：US865213

申请日：1977-12-28

申请人： Takemi Koeda ,  Takashi Tsuruoka ,  Hiroyasu Asaoka ,  Uichi Shibata ,  Shigeharu Inoue ,  Taro Niida

发明人： Takemi Koeda ,  Takashi Tsuruoka ,  Hiroyasu Asaoka ,  Uichi Shibata ,  Shigeharu Inoue ,  Taro Niida

IPC分类号： C07D213/79 ,  A61K31/44

CPC分类号： C07D213/79

摘要： Novel compounds useful as hypotensive agents are presented having the general formula I ##STR1## wherein R.sub.1 represents a substituted or unsubstituted aralkyl group, that is an aralkyl group of the general formula ##STR2## wherein R.sub.2 represents hydrogen, a lower alkyl group or a halogen atom. Furthermore, new therapeutic compositions of matter are also described incorporating the above novel 3-substituted-2(1H)pyridone-6-carboxylic acids (I) as an active ingredient with carriers and showing uses as hypotensive agents. These new compounds of the formula I are prepared by reacting D-glucaro-.delta.-lactam or its salt with an aralkyl halide.

摘要翻译： 提供了用作降压剂的新型化合物，其具有通式I（I），其中R 1表示取代或未取代的芳烷基，即通式为“IMAGE”的芳烷基，其中R 2表示氢，低级烷基 或卤素原子。 此外，还描述了新型的物质治疗组合物，其结合上述新型3-取代-2（1H）吡啶酮-6-羧酸（I）作为活性成分与载体并用作降压剂。 这些新的式I化合物通过D-葡聚糖-δ-内酰胺或其盐与芳烷基卤化物反应来制备。

公开(公告)号：US4083850A

公开(公告)日：1978-04-11

申请号：US700340

申请日：1976-06-28

申请人： Takemi Koeda ,  Takashi Tsuruoka ,  Hiroyasu Asaoka ,  Uichi Shibata ,  Shigeharu Inoue ,  Taro Niida

发明人： Takemi Koeda ,  Takashi Tsuruoka ,  Hiroyasu Asaoka ,  Uichi Shibata ,  Shigeharu Inoue ,  Taro Niida

IPC分类号： C07D213/79 ,  C07D213/55

CPC分类号： C07D213/79

摘要： Novel compounds useful as hypotensive agents are presented having the general formula I ##STR1## wherein R.sub.1 represents a lower aliphatic acyl group, a straight or branched chain alkyl or alkenyl group or an aralkyl group of the general formula ##STR2## wherein R.sub.2 represents hydrogen, a lower alkyl group or a halogen atom. Furthermore, new therapeutic compositions of matter are also described incorporating the above novel 3-substituted-2(1H)pyridone-6-carboxylic acids (I) as an active ingredient with carriers and showing uses as hypotensive agents. These new compounds of the formula I are prepared either by reacting D-glucaro-.delta.-lactam or its salt with an acid anhydride or by reacting 3-hydroxy-2(1H)pyridone-6-carboxylic acid with an acyl anhydride or alkyl halide, aralkyl halide and an alkenyl halide.

摘要翻译： 提供了可用作降压剂的新型化合物，其具有通式I（I），其中R 1表示低级脂族酰基，直链或支链烷基或烯基或通式为“IMAGE”的芳烷基，其中R 2 表示氢，低级烷基或卤素原子。 此外，还描述了新型的物质治疗组合物，其结合上述新型3-取代-2（1H）吡啶酮-6-羧酸（I）作为活性成分与载体并用作降压剂。 式I的这些新化合物通过D-葡聚糖-δ-内酰胺或其盐与酸酐反应或通过使3-羟基-2（1H）吡啶酮-6-羧酸与酰基酸酐或烷基卤化物 芳烷基卤化物和烯基卤化物。

公开(公告)号：US4198416A

公开(公告)日：1980-04-15

申请号：US944683

申请日：1978-09-22

申请人： Takemi Koeda ,  Takashi Tsuruoka ,  Uichi Shibata ,  Hiroyasu Asaoka ,  Mitsugu Hachisu ,  Osamu Itoh ,  Yasuharu Sekizawa ,  Shigeharu Inouye ,  Taro Niida

发明人： Takemi Koeda ,  Takashi Tsuruoka ,  Uichi Shibata ,  Hiroyasu Asaoka ,  Mitsugu Hachisu ,  Osamu Itoh ,  Yasuharu Sekizawa ,  Shigeharu Inouye ,  Taro Niida

IPC分类号： C07D213/65 ,  C07D213/79 ,  A61K31/44

CPC分类号： C07D213/79 ,  C07D213/65

摘要： 5-Alkoxy-picolinic esters represented by the formula (I): ##STR1## wherein R represents an alkyl group having 1 to 6 carbon atoms and R.sub.1 represents an unsubstituted phenyl group; a phenyl group substituted with one or more of an alkyl group having 1 to 4 carbon atoms or an acetyl group; a phthalidyl group; an alkoxyalkyl group wherein the alkyl moiety and the alkoxy moiety each has 1 to 4 carbon atoms; an alkoxyalkoxyalkyl group wherein the alkyl moiety and the alkoxy moiety each has 1 to 4 carbon atoms; an indanyl group; or an acyloxyalkyl group having the formula ##STR2## wherein R.sub.2 represents a hydrogen atom or a methyl group and R.sub.3 represents an alkyl group having 1 to 5 carbon atoms (such as a methyl, n-propyl, isobutyl, t-butyl, etc., group), an alkoxy group having 1 to 4 carbon atoms, a phenyl group, a phenyl group substituted with one or more of an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms or a halogen atom (such as chlorine, bromine, iodine, etc., atom) or an aralkyl group wherein the alkyl moiety has 1 to 3 carbon atoms, which are useful as anti-hypertensive agents, a process for preparing 5-alkoxy-picolinic esters, and anti-hypertensive compositions containing the 5-alkoxy-picolinic esters.

摘要翻译： 由式（I）表示的5-烷氧基 - 吡啶甲酸酯：其中R表示具有1至6个碳原子的烷基，R 1表示未取代的苯基; 被一个或多个具有1至4个碳原子的烷基或乙酰基取代的苯基; 苯酞基; 其中烷基部分和烷氧基部分各自具有1至4个碳原子的烷氧基烷基; 其中烷基部分和烷氧基部分各自具有1至4个碳原子的烷氧基烷氧基烷基; 茚满基; 或具有式“IMAGE”的酰氧基烷基，其中R 2表示氢原子或甲基，R 3表示具有1至5个碳原子的烷基（例如甲基，正丙基，异丁基，叔丁基等） ，基团），具有1至4个碳原子的烷氧基，苯基，被一个或多个具有1至4个碳原子的烷基取代的苯基，具有1至4个碳原子的烷氧基或卤素原子 （例如氯，溴，碘等原子）或其中烷基部分具有1〜3个碳原子的芳烷基，其可用作抗高血压剂，制备5-烷氧基 - 吡啶甲酸酯的方法和 含有5-烷氧基 - 吡啶甲酸酯的抗高血压组合物。

公开(公告)号：US4189489A

公开(公告)日：1980-02-19

申请号：US838180

申请日：1977-09-30

申请人： Takemi Koeda ,  Takashi Tsuruoka ,  Uichi Shibata ,  Hiroyasu Asaoka ,  Mitsugu Hachisu ,  Osamu Itoh ,  Yasuharu Sekizawa ,  Shigeharu Inouye ,  Taro Niida

发明人： Takemi Koeda ,  Takashi Tsuruoka ,  Uichi Shibata ,  Hiroyasu Asaoka ,  Mitsugu Hachisu ,  Osamu Itoh ,  Yasuharu Sekizawa ,  Shigeharu Inouye ,  Taro Niida

IPC分类号： A61K31/44 ,  A61P9/12 ,  C07D213/65 ,  C07D213/79 ,  A61K31/445 ,  C07D213/89

CPC分类号： C07D213/79 ,  C07D213/65

摘要： 5-Alkoxy-picolinic acids and the salts and the esters thereof represented by the formula (I): ##STR1## wherein R represents an alkyl group having 1 to 6 carbon atoms and M represents a hydrogen atom; a calcium atom; a sodium atom; a potassium atom; an aluminum atom; an unsubstituted phenyl group; a phenyl group substituted with one or more of an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms or a halogen atom (such as a chlorine, bromine, iodine, etc., atom); a phthalidyl group; an alkoxyalkyl group wherein the alkyl moiety and the alkoxy moiety each has 1 to 4 carbon atoms; or an acyloxyalkyl group having the formula ##STR2## wherein R.sub.2 represents a hydrogen atom or a methyl group and R.sub.3 represents an alkyl group having 1 to 5 carbon atoms (such as a methyl, n-propyl, isobutyl, t-butyl, etc., group), an alkoxy group having 1 to 4 carbon atoms, a phenyl group, a phenyl group substituted with one or more of an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms or a halogen atom (such as a chlorine, bromine, iodine, etc., atom) or an aralkyl group wherein the alkyl moiety has 1 to 3 carbon atoms, which are useful as anti-hypertensive agents, a process for preparing 5-alkoxy-picolinic acids and the salts and the esters thereof, and anti-hypertensive compositions containing the 5-alkoxy-picolinic acids and the salts and the esters thereof.

摘要翻译： 5-烷氧基 - 吡啶甲酸及其由式（I）表示的盐及其酯：其中R表示具有1至6个碳原子的烷基，M表示氢原子; 钙原子; 一个钠原子; 钾原子; 铝原子; 未取代的苯基; 被一个或多个具有1至4个碳原子的烷基，具有1至4个碳原子的烷氧基或卤素原子（例如氯，溴，碘等）原子取代的苯基; 苯酞基; 其中烷基部分和烷氧基部分各自具有1至4个碳原子的烷氧基烷基; 或具有式“IMAGE”的酰氧基烷基，其中R 2表示氢原子或甲基，R 3表示具有1至5个碳原子的烷基（例如甲基，正丙基，异丁基，叔丁基等） ，基团），具有1至4个碳原子的烷氧基，苯基，被一个或多个具有1至4个碳原子的烷基取代的苯基，具有1至4个碳原子的烷氧基或卤素原子 （例如氯，溴，碘等原子）或其中烷基部分具有1至3个碳原子的芳烷基，其可用作抗高血压剂，制备5-烷氧基 - 吡啶甲酸的方法和 其盐和酯，以及含有5-烷氧基 - 吡啶甲酸及其盐及其酯的抗高血压组合物。

公开(公告)号：US4229448A

公开(公告)日：1980-10-21

申请号：US23504

申请日：1979-03-23

申请人： Yasuharu Sekizawa ,  Takashi Tsuruoka ,  Mitsugu Hachisu ,  Masaji Sezaki ,  Masashi Miyamoto ,  Uichi Shibata ,  Kazuko Mizutani ,  Shigeharu Inouye ,  Takemi Koeda ,  Keizo Shimomura ,  Taro Niida

发明人： Yasuharu Sekizawa ,  Takashi Tsuruoka ,  Mitsugu Hachisu ,  Masaji Sezaki ,  Masashi Miyamoto ,  Uichi Shibata ,  Kazuko Mizutani ,  Shigeharu Inouye ,  Takemi Koeda ,  Keizo Shimomura ,  Taro Niida

IPC分类号： C07D213/65 ,  C07D213/79 ,  C07D213/81 ,  A61K31/455

CPC分类号： C07D213/79 ,  C07D213/65 ,  C07D213/81

摘要： 5-Substituted picolinic acid derivatives represented by the formula (I): ##STR1## wherein R.sub.1 represents a straight or branched chain halogen-substituted alkyl group having 2 to 6 carbon atoms or a substituted phenyl group having the formula ##STR2## wherein R.sub.3 and R.sub.4, which may be the same or different, each represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group, an amino group, an N-alkyl-substituted amino group, an acylamino group, an acetyl group, an acyloxy group, a hydroxy group or a halogen-substituted alkyl group or R.sub.3 and R.sub.4, when taken together, represent a polymethylene chain; and R.sub.2 represents an --OM group wherein M represents a hydrogen, sodium, potassium, calcium, aluminium or magnesium atom, a straight or branched chain or cyclic alkoxy group having 1 to 6 carbon atoms, an aminoalkoxy group, a phenoxy group, a substituted phenoxy group, a 5-indanyloxy group, an acyloxyalkyloxy group having the formula ##STR3## wherein R.sub.5 represents a hydrogen atom or a methyl group and R.sub.6 represents a lower alkyl group having 1 to 6 carbon atoms, a phenyl group or a substituted phenyl group, or an amino group represented by the formula ##STR4## wherein R.sub.7 and R.sub.8, which may be the same or different, each represents a hydrogen atom, a lower alkyl group, or a phenyl group which are useful as anti-hypertensive agents, a process for preparing the above 5-substituted picolinic acid derivatives, and anti-hypertensive compositions containing the same.

摘要翻译： 由式（I）表示的5-取代的吡啶甲酸衍生物：其中R 1表示具有2至6个碳原子的直链或支链卤素取代的烷基或具有下式的取代苯基： 其中可以相同或不同的R 3和R 4各自表示氢原子，卤素原子，低级烷基，低级烷氧基，硝基，氨基，N-烷基取代的氨基， 酰氨基，乙酰基，酰氧基，羟基或卤素取代的烷基，或者R 3和R 4一起表示聚亚甲基链; R 2表示-OM基，其中M表示氢，钠，钾，钙，铝或镁原子，具有1至6个碳原子的直链或支链或环状烷氧基，氨基烷氧基，苯氧基，取代的 苯氧基，5-茚满氧基，具有式“IMAGE”的酰氧基烷氧基，其中R5表示氢原子或甲基，R6表示碳原子数1〜6的低级烷基，苯基或取代苯基 或由式“IMAGE”表示的氨基，其中R7和R8可以相同或不同，表示可用作抗高血压剂的氢原子，低级烷基或苯基， 制备上述5-取代的吡啶甲酸衍生物的方法和含有它们的抗高血压组合物。

公开(公告)号：US5007438A

公开(公告)日：1991-04-16

申请号：US329914

申请日：1989-03-28

申请人： Shunro Tachibana ,  Uichi Shibata

发明人： Shunro Tachibana ,  Uichi Shibata

IPC分类号： A61H23/02 ,  A61M37/00

CPC分类号： A61H23/0245 ,  A61M37/0092 ,  A61H2201/105

摘要： Disclosed is an endermic application kit for external medicines, which comprises a drug-containing layer as provided near an ultrasonic oscillator. The kit includes a cylindrical fixed-type or portable-type and a flat regular-type or adhesive-type, and the adhesive-type may be flexible and elastic. The drug absorption is ensured by the action of the ultrasonic waves from the oscillator and the drug release can be controlled by varying the ultrasonic wave output from the oscillator.

公开(公告)号：US4821740A

公开(公告)日：1989-04-18

申请号：US120555

申请日：1987-11-13

申请人： Shunro Tachibana ,  Uichi Shibata

发明人： Shunro Tachibana ,  Uichi Shibata

IPC分类号： A61H23/02 ,  A61M37/00 ,  A61N1/00

CPC分类号： A61H23/0245 ,  A61M37/0092 ,  A61H2201/105

摘要： Disclosed is an endermic application kit for external medicines, which comprises a drug-containing layer as provided near an ultrasonic oscillator. The kit includes a cylindrical fixed-type or portable-type and a flat regular-type or adhesive-type, and the adhesive-type may be flexible and elastic. The drug absorption is ensured by the action of the ultrasonic waves from the oscillator and the drug release can be controlled by varying the ultrasonic wave output from the oscillator.

公开(公告)号：US4953565A

公开(公告)日：1990-09-04

申请号：US329913

申请日：1989-03-28

申请人： Shunro Tachibana ,  Uichi Shibata

发明人： Shunro Tachibana ,  Uichi Shibata

IPC分类号： A61H23/02 ,  A61M37/00

CPC分类号： A61H23/0245 ,  A61M37/0092 ,  A61H2201/105

摘要： An endermic application kit for external medicines comprises a container for retaining liquid containing drug, a device for supplying the liquid containing drug into the container, a drug permeable layer attached to the container to cover a bottom opening of the container, and an ultrasonic oscillator situated inside the container. When the ultrasonic oscillator and supplying device are actuated, the liquid containing drug is continuously supplied to the container, and the drug contained in the liquid is applied to a skin of a patient through the drug permeable layer by means of the ultrasonic oscillator.