公开(公告)号：US20050171196A1

公开(公告)日：2005-08-04

申请号：US10503215

申请日：2003-01-30

申请人： Akihito Fujii ,  Toshiyuki Negoro ,  Chiaki Migihashi ,  Makoto Murata ,  Keiji Nakamura ,  Takashi Nukuda ,  Takafumi Matsumoto ,  Kiyomi Imano

发明人： Akihito Fujii ,  Toshiyuki Negoro ,  Chiaki Migihashi ,  Makoto Murata ,  Keiji Nakamura ,  Takashi Nukuda ,  Takafumi Matsumoto ,  Kiyomi Imano

IPC分类号： A61K31/341 ,  A61K31/381 ,  A61K31/40 ,  A61K31/404 ,  A61K31/443 ,  A61K31/4709 ,  A61K31/5377 ,  A61P1/00 ,  A61P1/18 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P43/00 ,  C07D307/68 ,  A61K31/34 ,  C07D307/02

CPC分类号： C07D405/12 ,  A61K31/341 ,  A61K31/381 ,  A61K31/40 ,  A61K31/404 ,  A61K31/443 ,  A61K31/4709 ,  A61K31/5377 ,  C07D307/68 ,  C07D405/04 ,  C07D407/12 ,  C07D407/14 ,  C07D409/04 ,  C07D409/12

摘要： The present invention provides 2-furancarboxylic acid hydrazide compounds represented by General Formula (I) below, and prodrugs, physiologically acceptable salts, hydrates, solvates thereof, methods for producing them and pharmaceutical compositions containing them: wherein A is a group represented by Formula (a) or the like: (wherein either R4 or R5 represents cyano, nitro or the like, and the other represents a hydrogen atom or the like); either R1 or R2 represents a group: -D-(X)m-R6 or the like, and the other represents a group: -E-(Y)n-R7, hydrogen atom, aryl or the like; R3 is a hydrogen atom or the like; D and E independently represent aryl; X and Y independently represent O or the like; R6 and R7 independently represent alkyl, aryl, arylalkyl or the like; and m and n are independently 0 or 1, provided that the aryl is optionally substituted. Such compounds exhibit a potent antagonistic activity on glucagon receptor and are of use as preventive and/or therapeutic agents for symptoms and diseases in which glucagon is involved.

摘要翻译： 本发明提供由下述通式（I）表示的2-呋喃甲酰肼化合物及其前体药物，生理学上可接受的盐，水合物，溶剂化物，其制备方法和含有它们的药物组合物：其中A是由式 a）等：（其中R 4或R 5或R 5表示氰基，硝基等，另一个表示氢原子等）; R 1或R 2 2代表基团：-D-（X）m R 6等，另一个表示一个基团： -E-（Y）nR 7，氢原子，芳基等; R 3是氢原子等; D和E独立地表示芳基; X和Y独立地表示O等; R 6和R 7独立地代表烷基，芳基，芳烷基等; 并且m和n独立地为0或1，条件是芳基任选被取代。 这些化合物对胰高血糖素受体表现出有效的拮抗活性，并且可用作涉及胰高血糖素的症状和疾病的预防和/或治疗剂。

公开(公告)号：US5258382A

公开(公告)日：1993-11-02

申请号：US901029

申请日：1992-06-19

申请人： Toshiyuki Negoro ,  Makoto Murata ,  Shozo Ueda ,  Buichi Fujitani ,  Yoshiyuki Ono

发明人： Toshiyuki Negoro ,  Makoto Murata ,  Shozo Ueda ,  Buichi Fujitani ,  Yoshiyuki Ono

IPC分类号： A61K31/495 ,  A61P3/08 ,  A61P3/10 ,  C07D207/416 ,  C07D487/20 ,  C12N9/99

CPC分类号： C07D487/20 ,  Y02P20/55

摘要： Tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3'-pyrrolidine derivatives of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are independently hydrogen, halogen, trifluoromethyl, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, or nitro, and R.sup.3 is hydrogen, halogen or alkyl having 1 to 6 carbon atoms, and pharmaceutically acceptable salts thereof, processes for preparation thereof, and pharmaceutical composition containing the same. Said compounds and their salts show excellent aldose reductase inhibitory activity and are useful for the prevention and treatment of diabetic complications.

公开(公告)号：US08415487B2

公开(公告)日：2013-04-09

申请号：US13239731

申请日：2011-09-22

申请人： Daisuke Tanaka ,  Toshiyuki Negoro

发明人： Daisuke Tanaka ,  Toshiyuki Negoro

IPC分类号： C07D207/444

CPC分类号： C07D207/416

摘要： The present invention is a process for preparing (3R)-2′-(4-bromo-2-fluorobenzyl)spiro-[pyrrolidine-3,4′(1′H)-pyrrolo[1,2-a]pyrazine]-1′,2,3′,5(2H′)-tetraone, comprising, for example, the following steps: (1) reacting a compound of the formula (III) wherein R is a C1-6 alkyl group, with 2,5-dimethoxytetrahydrofuran to provide a compound of the formula (IV) wherein R is a C1-6 alkyl group; (2) reacting the compound of the formula (IV) wherein R is a C1-6 alkyl group, with trichloroacetyl chloride to provide a compound of the formula wherein R is a C1-6 group; and (3) reacting the compound provided in step (2) with 4-bromo-2-fluorobenzylamine to provide (3R)-2′-(4-bromo-2-fluorobenzyl)spiro-[pyrrolidine-3,4′(1′H)-pyrrolo[1,2-a]pyrazine]-1′,2,3′,5(2H′)-tetraone.

摘要翻译： 本发明是制备（3R）-2' - （4-溴-2-氟苄基）螺 - [吡咯烷-3,4'（1'H） - 吡咯并[1,2-a]吡嗪] 1'，2,3'，5（2H'） - 四酮，包括例如以下步骤：（1）使其中R为C 1-6烷基的式（III）化合物与2， 得到其中R为C 1-6烷基的式（Ⅳ）化合物; （2）使其中R为C1-6烷基的式（Ⅳ）化合物与三氯乙酰氯反应，得到下式的化合物其中R为C1-6基团; 和（3）使步骤（2）中提供的化合物与4-溴-2-氟苄胺反应，得到（3R）-2' - （4-溴-2-氟苄基）螺 - [吡咯烷-3,4'（1 H' - 吡咯并[1,2-a]吡嗪] -1'，2,3'，5（2H'） - 四酮。

公开(公告)号：US08058456B2

公开(公告)日：2011-11-15

申请号：US12309104

申请日：2007-06-13

申请人： Daisuke Tanaka ,  Toshiyuki Negoro

发明人： Daisuke Tanaka ,  Toshiyuki Negoro

IPC分类号： C07D295/22

CPC分类号： C07D207/416

摘要： The present invention provides a compound of the formula (III): wherein R is a C1-6 alkyl group, as a novel optically active intermediate for preparing tetrahydropyrrolo[1,2-a]pyrazin-4-spiro-3′-pyrrolidine derivatives such as Ranirestat being a promising therapeutic agent for diabetic complications in a short process, in an economically advantageous manner and in high yields, and the process for preparing the same.

摘要翻译： 作为制备四氢吡咯并[1,2-a]吡嗪-4-螺-3'-吡咯烷衍生物的新的光学活性中间体，本发明提供式（III）的化合物：其中R是C1-6烷基 例如，在经济上有利的方式和高产率下，兰尼斯特是一种有希望的治疗糖尿病并发症的治疗剂，以及其制备方法。

公开(公告)号：US07514452B2

公开(公告)日：2009-04-07

申请号：US10503215

申请日：2003-01-30

申请人： Akihito Fujii ,  Toshiyuki Negoro ,  Chiaki Migihashi ,  Makoto Murata ,  Keiji Nakamura ,  Takashi Nukuda ,  Takafumi Matsumoto ,  Kiyomi Imano

发明人： Akihito Fujii ,  Toshiyuki Negoro ,  Chiaki Migihashi ,  Makoto Murata ,  Keiji Nakamura ,  Takashi Nukuda ,  Takafumi Matsumoto ,  Kiyomi Imano

IPC分类号： A61K31/47 ,  C07D307/02 ,  C07D405/00

CPC分类号： C07D405/12 ,  A61K31/341 ,  A61K31/381 ,  A61K31/40 ,  A61K31/404 ,  A61K31/443 ,  A61K31/4709 ,  A61K31/5377 ,  C07D307/68 ,  C07D405/04 ,  C07D407/12 ,  C07D407/14 ,  C07D409/04 ,  C07D409/12

摘要： The present invention provides 2-furancarboxylic acid hydrazide compounds represented by General Formula (I) below, and prodrugs, physiologically acceptable salts, hydrates, solvates thereof: wherein A is a group represented by Formula (a) or the like: (wherein either R4 or R5 represents cyano, nitro or the like, and the other represents a hydrogen atom or the like); either R1 or R2 represents a group: -D-(X)m-R6 or the like, and the other represents a group: -E-(Y)n-R7, hydrogen atom, aryl or the like; R3 is a hydrogen atom or the like; D and E independently represent aryl; X and Y independently represent O or the like; R6 and R7 independently represent alkyl, aryl, arylalkyl or the like; and m and n are independently 0 or 1, provided that the aryl is optionally substituted.

摘要翻译： 本发明提供由下述通式（I）表示的2-呋喃甲酰肼化合物及其前药，生理学上可接受的盐，水合物，溶剂合物：其中A为由式（a）等表示的基团：（其中R 4 或R 5表示氰基，硝基等，另一个表示氢原子等）。 R 1或R 2表示基团：-D-（X）m -R 6等，另一个表示基团：-E-（Y）n -R 7，氢原子，芳基等; R3是氢原子等; D和E独立地表示芳基; X和Y独立地表示O等; R6和R7独立地表示烷基，芳基，芳烷基等; 并且m和n独立地为0或1，条件是芳基任选被取代。

公开(公告)号：US20120010405A1

公开(公告)日：2012-01-12

申请号：US13239731

申请日：2011-09-22

申请人： Daisuke Tanaka ,  Toshiyuki Negoro

发明人： Daisuke Tanaka ,  Toshiyuki Negoro

IPC分类号： C07D487/20 ,  C07D207/416 ,  C07D403/04

CPC分类号： C07D207/416

摘要： The present invention provides a compound of the formula (III): wherein R is a C1-6 alkyl group, as a novel optically active intermediate for preparing tetrahydropyrrolo[1,2-a]pyrazin-4-spiro-3′-pyrrolidine derivatives such as Ranirestat being a promising therapeutic agent for diabetic complications in a short process, in an economically advantageous manner and in high yields, and the process for preparing the same.

摘要翻译： 作为制备四氢吡咯并[1,2-a]吡嗪-4-螺-3'-吡咯烷衍生物的新的光学活性中间体，本发明提供式（III）的化合物：其中R是C1-6烷基 例如，在经济上有利的方式和高产率下，兰尼斯特是一种有希望的治疗糖尿病并发症的治疗剂，以及其制备方法。

公开(公告)号：US20090286980A1

公开(公告)日：2009-11-19

申请号：US12309104

申请日：2007-06-13

申请人： Daisuke Tanaka ,  Toshiyuki Negoro

发明人： Daisuke Tanaka ,  Toshiyuki Negoro

IPC分类号： C07D405/06 ,  C07D207/30 ,  C07D237/00

CPC分类号： C07D207/416

摘要： The present invention provides a compound of the formula (III): wherein R is a C1-6 alkyl group, as a novel optically active intermediate for preparing tetrahydropyrrolo[1,2-a]pyrazin-4-spiro-3′-pyrrolidine derivatives such as Ranirestat being a promising therapeutic agent for diabetic complications in a short process, in an economically advantageous manner and in high yields, and the process for preparing the same.

摘要翻译： 作为制备四氢吡咯并[1,2-a]吡嗪-4-螺-3'-吡咯烷衍生物的新的光学活性中间体，本发明提供式（III）的化合物：其中R是C1-6烷基 例如，在经济上有利的方式和高产率下，兰尼斯特是一种有希望的治疗糖尿病并发症的治疗剂，以及其制备方法。