公开(公告)号：US20060217556A1

公开(公告)日：2006-09-28

申请号：US10553034

申请日：2004-04-14

申请人： Junichiro Uda ,  Tomomitsu Sasaki ,  Takahiro Sato ,  Tsutomu Inoue

发明人： Junichiro Uda ,  Tomomitsu Sasaki ,  Takahiro Sato ,  Tsutomu Inoue

IPC分类号： A61K31/4741 ,  C07D491/02

CPC分类号： C07D491/04 ,  A61K31/553

摘要： Provided are a process for producing an acid addition salt of a 3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid alkyl ester by reacting a 3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid alkyl ester with an acid, and a process for producing 3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid using the acid addition salt as an intermediate. By using as an intermediate an acid addition salt of a 3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid alkyl ester to produce 3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11-ylidene)piperidino]propionic acid, the metals used in the synthetic reaction steps and the organic compounds mainly by-produced during production are readily separated from a reaction liquid by a simple procedure, and the by-products are sufficiently removed without using a purification step by chromatography, thereby enabling mass production and enhancing production efficiency.

摘要翻译： 提供了制备3- [4-（8-氟-5,11-二氢苯并[b]氧杂环庚烯并[4,3-b]吡啶-11-亚基）哌啶子基]丙酸烷基酯的酸加成盐的方法 通过使3- [4-（8-氟-5,11-二氢苯并[b]氧杂环庚烯并[4,3-b]吡啶-11-亚基）哌啶子基]丙酸烷基酯与酸反应， 使用酸加成盐作为中间体的3- [4-（8-氟-5,11-二氢苯并[b]氧杂环庚烯并[4,3-b]吡啶-11-亚基）哌啶子基]丙酸。 通过使用3- [4-（8-氟-5,11-二氢苯并[b]氧杂环庚烯并[4,3-b]吡啶-11-亚基）哌啶子基]丙酸烷基酯的酸加成盐 制备3- [4-（8-氟-5,11-二氢苯并[b]氧杂环庚烯并[4,3-b]吡啶]亚基）哌啶子基]丙酸，合成反应步骤中使用的金属和有机化合物 主要通过简单的方法容易地从生产中副产的副产物与反应液分离，并且副产物被充分除去，而不需要通过色谱法的纯化步骤，从而可以批量生产并提高生产效率。

公开(公告)号：US20060189811A1

公开(公告)日：2006-08-24

申请号：US10565678

申请日：2004-07-23

申请人： Hiroshi Nakamura ,  Junichiro Uda ,  Atsushi Ohno ,  Takahiro Sato

发明人： Hiroshi Nakamura ,  Junichiro Uda ,  Atsushi Ohno ,  Takahiro Sato

IPC分类号： C07D403/14

CPC分类号： C07D403/14

摘要： Provided is a process for producing 1,2,4-triazole compound (5), or a salt or hydrate thereof which comprises reacting compound (1) with Rc-X (2) to give compound (3), reacting compound (3) with a nitrilization agent to give compound (4), and then removing the group Rc, as shown by the reaction scheme: (Wherein Ra, Rb and Rd represent a group, Rc represents a group which can be removed by an acid) A 1,2,4-triazole compound (5) having an optionally substituted 2-cyanopyridin-4-yl group at 3-position and an optionally substituted aromatic group at 5-position which inhibits a xanthine oxidase and is useful for treatment of gout and hyperuricemia can be obtained from compound (1) in a high yield without requiring isolation of reaction products in the course of reactions.

摘要翻译： 本发明提供了使化合物（1）与Rc-X（2）反应得到化合物（3），使化合物（3）与化合物（3）反应的1,2,4-三唑化合物（5）或其盐或水合物的方法， 与硝化剂反应得到化合物（4），然后除去Rc基团，如反应方案所示：（其中Ra，Rb和Rd表示基团，Rc表示可被酸除去的基团）A 1 ，3位具有任选取代的2-氰基吡啶-4-基的2,4-三唑化合物（5）和5位上任意取代的芳族基团，其抑制黄嘌呤氧化酶并且可用于治疗痛风和高尿酸血症 可以以高产率从化合物（1）获得，而不需要在反应过程中分离反应产物。

公开(公告)号：US08367843B2

公开(公告)日：2013-02-05

申请号：US13499190

申请日：2010-09-29

申请人： Seiichi Kobashi ,  Junichiro Uda ,  Sachiho Miyata ,  Tsutomu Inoue ,  Naoki Ashizawa ,  Koji Matsumoto ,  Tetsuya Taniguchi ,  Takashi Iwanaga ,  Osamu Nagata

发明人： Seiichi Kobashi ,  Junichiro Uda ,  Sachiho Miyata ,  Tsutomu Inoue ,  Naoki Ashizawa ,  Koji Matsumoto ,  Tetsuya Taniguchi ,  Takashi Iwanaga ,  Osamu Nagata

IPC分类号： A61K31/428 ,  C07D277/62

CPC分类号： C07D277/62 ,  C07D417/02 ,  C07D417/10

摘要： Disclosed are a novel compound and a pharmaceutical product, each having a remarkable uricosuric effect. Specifically disclosed are: a novel phenol derivative represented by general formula (1) that is shown in FIG. 1; a pharmaceutically acceptable salt thereof; a hydrate of the derivative or the salt; and a solvate of the derivative or the salt. (In the formula, R1 and R2 may be the same or different and each represents a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower alkoxy group, a haloalkyl group, a haloalkoxy group, an alkylsulfanyl group, an alkylsulfinyl group, an alkylsulfonyl group, a lower alkyl-substituted carbamoyl group, a saturated nitrogen-containing heterocyclic N-carbonyl group, a halogen atom, a cyano group or a hydrogen atom; R3 represents a lower alkyl group, a haloalkyl group, a halogen atom, a hydroxy group or a hydrogen atom; and X represents a sulfur atom, an —S(═O)— group or an —S(═O)2— group.)

摘要翻译： 公开了一种新型化合物和药物，其具有显着的尿酸营养作用。 具体公开的是：图1所示的通式（1）表示的新型苯酚衍生物。 1; 其药学上可接受的盐; 衍生物或盐的水合物; 和衍生物或盐的溶剂化物。 （式中，R 1，R 2可以相同或不同，表示低级烷基，低级烯基，低级炔基，低级烷氧基，卤代烷基，卤代烷氧基，烷基硫烷基， 烷基亚磺酰基，烷基磺酰基，低级烷基取代氨基甲酰基，饱和含氮杂环N-羰基，卤素原子，氰基或氢原子; R3表示低级烷基，卤代烷基， 卤素原子，羟基或氢原子; X表示硫原子，-S（= O） - 基或-S（= O）2 - 基）。

公开(公告)号：US20120184587A1

公开(公告)日：2012-07-19

申请号：US13499190

申请日：2010-09-29

申请人： Seiichi Kobashi ,  Junichiro Uda ,  Sachiho Miyata ,  Tsutomu Inoue ,  Naoki Ashizawa ,  Koji Matsumoto ,  Tetsuya Taniguchi ,  Takashi Iwanaga ,  Osamu Nagata

发明人： Seiichi Kobashi ,  Junichiro Uda ,  Sachiho Miyata ,  Tsutomu Inoue ,  Naoki Ashizawa ,  Koji Matsumoto ,  Tetsuya Taniguchi ,  Takashi Iwanaga ,  Osamu Nagata

IPC分类号： A61K31/428 ,  C07D417/10 ,  A61P7/00 ,  A61P3/04 ,  A61P19/06 ,  A61P3/10 ,  A61P9/12 ,  A61P9/10 ,  A61P7/02 ,  C07D277/62 ,  A61P3/06

CPC分类号： C07D277/62 ,  C07D417/02 ,  C07D417/10

摘要： Disclosed are a novel compound and a pharmaceutical product, each having a remarkable uricosuric effect. Specifically disclosed are: a novel phenol derivative represented by general formula (1) that is shown in FIG. 1; a pharmaceutically acceptable salt thereof; a hydrate of the derivative or the salt; and a solvate of the derivative or the salt. (In the formula, R1 and R2 may be the same or different and each represents a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower alkoxy group, a haloalkyl group, a haloalkoxy group, an alkylsulfanyl group, an alkylsulfinyl group, an alkylsulfonyl group, a lower alkyl-substituted carbamoyl group, a saturated nitrogen-containing heterocyclic N-carbonyl group, a halogen atom, a cyano group or a hydrogen atom; R3 represents a lower alkyl group, a haloalkyl group, a halogen atom, a hydroxy group or a hydrogen atom; and X represents a sulfur atom, an —S(═O)— group or an —S(═O)2— group.)

摘要翻译： 公开了一种新型化合物和药物，其具有显着的尿酸营养作用。 具体公开的是：图1所示的通式（1）表示的新型苯酚衍生物。 1; 其药学上可接受的盐; 衍生物或盐的水合物; 和衍生物或盐的溶剂化物。 （式中，R 1，R 2可以相同或不同，表示低级烷基，低级烯基，低级炔基，低级烷氧基，卤代烷基，卤代烷氧基，烷基硫烷基， 烷基亚磺酰基，烷基磺酰基，低级烷基取代氨基甲酰基，饱和含氮杂环N-羰基，卤素原子，氰基或氢原子; R3表示低级烷基，卤代烷基， 卤素原子，羟基或氢原子; X表示硫原子，-S（= O） - 基或-S（= O）2 - 基）。

公开(公告)号：US08148421B2

公开(公告)日：2012-04-03

申请号：US12440540

申请日：2007-09-10

申请人： Hideo Kato ,  Osamu Nagata ,  Yoshiyuki Iwabuchi ,  Takahiro Sato ,  Junichiro Uda ,  Tutomu Inoue ,  Hiroshi Nakamura ,  Nobuhide Kawasaki ,  Ippei Tanaka ,  Naoki Kurita ,  Tomohiko Ishikawa

发明人： Hideo Kato ,  Osamu Nagata ,  Yoshiyuki Iwabuchi ,  Takahiro Sato ,  Junichiro Uda ,  Tutomu Inoue ,  Hiroshi Nakamura ,  Nobuhide Kawasaki ,  Ippei Tanaka ,  Naoki Kurita ,  Tomohiko Ishikawa

IPC分类号： A61K31/382 ,  C07D335/02

CPC分类号： C07D335/02 ,  C07D333/24 ,  C07D333/28 ,  C07D333/32 ,  C07D333/38 ,  C07D333/48

摘要： A compound represented by the formula (1) or a salt thereof ( represents a single bond, or a double bond; R1 represents hydrogen atom, or an alkyl group; R2 and R3 represent hydrogen atom, or an alkyl group; R4 and R5 represent hydrogen atom, hydroxy group, an alkoxyl group, a halogen atom, or a mono- or di-alkyl-substituted amino group; R6 represents hydrogen atom, cyano group, an alkoxycarbonyl group, or carboxy group; R7 represents one or two of substituents on the benzene ring (the substituents are selected from hydrogen atom, a halogen atom, nitro group, cyano group, hydroxy group, amino group, an alkyl group, and an alkoxyl group); A represents a 5-membered or 6-membered non-aromatic heterocyclic ring containing one or two contiguous sulfur atoms (the sulfur atoms may independently form oxide); W represents oxo group, hydrogen atom, an alkyl group, hydroxy group, an alkoxyl group, or a halogen atom; and X represents oxygen atom, or sulfur atom), or a salt thereof, which has a superior suppressing action against prostaglandin E2 production and is useful as an active ingredient of medicaments with reduced adverse reactions such as gastrointestinal disorders.

摘要翻译： 由式（1）表示的化合物或其盐（表示单键或双键; R1表示氢原子或烷基; R2和R3表示氢原子或烷基; R4和R5表示 氢原子，羟基，烷氧基，卤素原子或一或二烷基取代的氨基; R 6表示氢原子，氰基，烷氧基羰基或羧基; R 7表示一个或两个取代基 在苯环上（取代基选自氢原子，卤素原子，硝基，氰基，羟基，氨基，烷基和烷氧基）; A表示5元或6元非 含有一个或两个相邻硫原子的杂环（硫原子可以独立地形成氧化物）; W表示氧代基，氢原子，烷基，羟基，烷氧基或卤素原子; X表示氧原子 ，或硫原子）或其盐 对前列腺素E2产生的抑制作用较差，并且可用作具有减少的不良反应如胃肠道疾病的药物的活性成分。

公开(公告)号：US20100048666A1

公开(公告)日：2010-02-25

申请号：US12440540

申请日：2007-09-10

申请人： Hideo Kato ,  Osamu Nagata ,  Yoshiyuki Iwabuchi ,  Takahiro Sato ,  Junichiro Uda ,  Tutomu Inoue ,  Hiroshi Nakamura ,  Nobuhide Kawasaki ,  Ippei Tanaka ,  Naoki Kurita ,  Tomohiko Ishikawa

发明人： Hideo Kato ,  Osamu Nagata ,  Yoshiyuki Iwabuchi ,  Takahiro Sato ,  Junichiro Uda ,  Tutomu Inoue ,  Hiroshi Nakamura ,  Nobuhide Kawasaki ,  Ippei Tanaka ,  Naoki Kurita ,  Tomohiko Ishikawa

IPC分类号： A61K31/382 ,  C07D335/02 ,  A61K31/381 ,  C07D333/38 ,  C07D333/32 ,  A61P13/02 ,  A61P13/08 ,  A61P13/10 ,  A61P3/10 ,  A61P35/00

CPC分类号： C07D335/02 ,  C07D333/24 ,  C07D333/28 ,  C07D333/32 ,  C07D333/38 ,  C07D333/48

摘要： A compound represented by the formula (1) or a salt thereof ( represents a single bond, or a double bond; R1 represents hydrogen atom, or an alkyl group; R2 and R3 represent hydrogen atom, or an alkyl group; R4 and R5 represent hydrogen atom, hydroxy group, an alkoxyl group, a halogen atom, or a mono- or di-alkyl-substituted amino group; R6 represents hydrogen atom, cyano group, an alkoxycarbonyl group, or carboxy group; R7 represents one or two of substituents on the benzene ring (the substituents are selected from hydrogen atom, a halogen atom, nitro group, cyano group, hydroxy group, amino group, an alkyl group, and an alkoxyl group); A represents a 5-membered or 6-membered non-aromatic heterocyclic ring containing one or two contiguous sulfur atoms (the sulfur atoms may independently form oxide); W represents oxo group, hydrogen atom, an alkyl group, hydroxy group, an alkoxyl group, or a halogen atom; and X represents oxygen atom, or sulfur atom), or a salt thereof, which has a superior suppressing action against prostaglandin E2 production and is useful as an active ingredient of medicaments with reduced adverse reactions such as gastrointestinal disorders.

摘要翻译： 由式（1）表示的化合物或其盐（表示单键或双键; R1表示氢原子或烷基; R2和R3表示氢原子或烷基; R4和R5表示 氢原子，羟基，烷氧基，卤素原子或一或二烷基取代的氨基; R 6表示氢原子，氰基，烷氧基羰基或羧基; R 7表示一个或两个取代基 在苯环上（取代基选自氢原子，卤素原子，硝基，氰基，羟基，氨基，烷基和烷氧基）; A表示5元或6元非 含有一个或两个相邻硫原子的杂环（硫原子可以独立地形成氧化物）; W表示氧代基，氢原子，烷基，羟基，烷氧基或卤素原子; X表示氧原子 ，或硫原子）或其盐 对前列腺素E2产生的抑制作用较差，并且可用作具有减少的不良反应如胃肠道疾病的药物的活性成分。

公开(公告)号：US06348461B1

公开(公告)日：2002-02-19

申请号：US09485716

申请日：2000-03-01

申请人： Yasuo Takano ,  Futoshi Shiga ,  Masanori Takadoi ,  Hideharu Uchiki ,  Jun Asano ,  Tsuyoshi Anraku ,  Kazunori Fukuchi ,  Junichiro Uda ,  Naoki Ando

发明人： Yasuo Takano ,  Futoshi Shiga ,  Masanori Takadoi ,  Hideharu Uchiki ,  Jun Asano ,  Tsuyoshi Anraku ,  Kazunori Fukuchi ,  Junichiro Uda ,  Naoki Ando

IPC分类号： C07D24144

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D241/44 ,  C07D249/08 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14

摘要： The present invention provides 6,7-asymmetrically disubstituted quinoxalinecarboxylic acid compounds and their addition salts, and processes for preparing them, which have antagonism against excitatory amino acid receptors, in particular, an AMPA receptor. The 6,7-asymmetrically disubstituted quinoxalinecarboxylic acid compounds and their addition salts of the present invention are represented by formula (1) wherein Q, R, R1 and R2 are as described in the specification.

摘要翻译： 本发明提供对兴奋性氨基酸受体，特别是AMPA受体具有拮抗作用的6,7-不对称二取代的喹喔啉羧酸化合物及其加成盐及其制备方法。 本发明的6,7-不对称二取代的喹喔啉羧酸化合物及其加成盐由式（1）表示，其中Q，R，R 1和R 2如说明书中所述。