公开(公告)号：US09040693B2

公开(公告)日：2015-05-26

申请号：US12089674

申请日：2006-10-17

申请人： Kohsuke Ohno ,  Takashi Miyagi ,  Tomonaga Ozawa ,  Nobuhiko Fushimi

发明人： Kohsuke Ohno ,  Takashi Miyagi ,  Tomonaga Ozawa ,  Nobuhiko Fushimi

IPC分类号： C07D495/04

CPC分类号： C07D495/04

摘要： The present invention provides a compound useful as an agent for the prevention or treatment of a sex hormone-dependent disease or the like. That is, the present invention provides a fused heterocyclic derivative represented by the following general formula (I), a pharmaceutical composition containing the same, a medicinal use thereof and the like. In the formula (I), ring A represents 5-membered cyclic unsaturated hydrocarbon or 5-membered heteroaryl; RA represents halogen, alkyl, alkenyl, alkynyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl or the like ; ring B represents aryl or heteroaryl; RB represents halogen, alkyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl or the like; E1 and E2 represent an oxygen atom or the like; U represents a single bond or alkylene; X represents a group represented by Y, —SO2—Y, —O—(alkylene)—Y, —O—Z in which Y represents Z, amino or the like; Z represents cycloalkyl, heterocycloalkyl, aryl, heteroaryl or the like; or the like.

摘要翻译： 本发明提供了可用作预防或治疗性激素依赖性疾病等的药剂的化合物。 也就是说，本发明提供由以下通式（I）表示的稠合杂环衍生物，含有该杂环衍生物的药物组合物，其医药用途等。 在式（I）中，环A表示5元环状不饱和烃或5元杂芳基; 烷基，烯基，炔基，羧基，烷氧基，氨基甲酰基，烷基氨基甲酰基等; 环B表示芳基或杂芳基; RB代表卤素，烷基，羧基，烷氧基，氨基甲酰基，烷基氨基甲酰基等; E1和E2表示氧原子等; U表示单键或亚烷基; X表示Y表示的基团，-SO 2 -Y，-O-（亚烷基）-Y，-O-Z，Y表示Z，氨基等; Z表示环烷基，杂环烷基，芳基，杂芳基等; 或类似物。

公开(公告)号：US08426427B2

公开(公告)日：2013-04-23

申请号：US12595931

申请日：2008-04-16

申请人： Kohsuke Ohno ,  Noboru Kamada

发明人： Kohsuke Ohno ,  Noboru Kamada

IPC分类号： C07D495/04 ,  A61K31/519 ,  A61P25/28 ,  A61P35/00

CPC分类号： C07D495/04

摘要： The present invention provides compounds useful as agents for the prevention or treatment of a sex hormone-dependent disease or the like. That is, the present invention provides fused heterocyclic derivatives represented by the following general formula (I) which has a GnRH antagonistic activity, pharmaceutical compositions containing the same, medicinal uses thereof and the like. In the formula (I), rings A is 5-membered cyclic unsaturated hydrocarbon or 5-membered heteroaryl; RA is halogen, alkyl, alkenyl, alkynyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl, etc.; ring B is aryl or heteroaryl; RB is halogen, alkyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl, etc.; E1 and E2 are oxygen atom, etc.; Q is hydrogen atom, alkyl, alkylsulfonyl, acyl, etc.; X is -(alkylene)-Z, —CO—Y, —SO2—Y, etc. (in which Y is Z or amino, etc.; Z is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, etc.

摘要翻译： 本发明提供了可用作预防或治疗性激素依赖性疾病等的试剂的化合物。 也就是说，本发明提供具有GnRH拮抗活性的由以下通式（I）表示的稠合杂环衍生物，含有它们的药物组合物，其药用用途等。 在式（I）中，环A是5元环状不饱和烃或5元杂芳基; RA是卤素，烷基，烯基，炔基，羧基，烷氧基，氨基甲酰基，烷基氨基甲酰基等; 环B是芳基或杂芳基; RB是卤素，烷基，羧基，烷氧基，氨基甲酰基，烷基氨基甲酰基等; E1和E2是氧原子等; Q是氢原子，烷基，烷基磺酰基，酰基等; X是 - （亚烷基）-Z，-CO-Y，-SO2-Y等（其中Y是Z或氨基等; Z是环烷基，杂环烷基，芳基，杂芳基等）

公开(公告)号：US20090054356A1

公开(公告)日：2009-02-26

申请号：US11816056

申请日：2006-02-14

申请人： Nobuhiko Fushimi ,  Shigeru Yonekubo ,  Kohsuke Ohno

发明人： Nobuhiko Fushimi ,  Shigeru Yonekubo ,  Kohsuke Ohno

IPC分类号： A61K31/7056 ,  C07H17/02 ,  A61K45/00 ,  A61P3/00 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P5/48 ,  A61P7/10 ,  A61P9/10 ,  A61P9/12 ,  A61P19/06

CPC分类号： A61K45/06 ,  A61K31/7056 ,  C07H17/02

摘要： [Objective] The present invention provides a compound having an SGLT1 and/or SGLT2 inhibitory activity which is usable as an agent for the prevention or treatment of diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications, obesity or the like. [Means to Solve the Problem] It is a 1-substituted-7-(β-D-glycopyranosyloxy)(aza)-indole compound represented by the general formula (I), a prodrug thereof, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof: wherein R1 represents a halogen atom or the like; n represents j an integer number from 0 to 3; R2 represents a hydrogen atom or the like; X represents a carbon atom which a hydrogen atom or the like binds to, or a nitrogen atom; Q represents an alkylene group or an alkenylene group each of which may have an oxygen atom or a sulfur atom in the chain; and A represents an aryl or heteroaryl group which may have a substituent.

摘要翻译： [目的]本发明提供具有SGLT1和/或SGLT2抑制活性的化合物，其可用作预防或治疗糖尿病，餐后高血糖症，葡萄糖耐量降低，糖尿病并发症，肥胖症等。 解决问题的方法是由通式（I）表示的1-取代-7-（β-D-吡喃糖基氧基）（氮杂） - 吲哚化合物，其前药或其药学上可接受的盐，或 其水合物或溶剂化物：其中R1表示卤素原子等; n表示j为0〜3的整数; R2表示氢原子等; X表示与氢原子等结合的碳原子或氮原子; Q表示可以在链中具有氧原子或硫原子的亚烷基或亚烯基; A表示可以具有取代基的芳基或杂芳基。

公开(公告)号：US20080139484A1

公开(公告)日：2008-06-12

申请号：US11576204

申请日：2005-09-28

申请人： Hirotaka Teranishi ,  Norihiko Kikuchi ,  Kohsuke Ohno

发明人： Hirotaka Teranishi ,  Norihiko Kikuchi ,  Kohsuke Ohno

IPC分类号： A61K31/7056 ,  C07H17/02 ,  A61P3/10 ,  A61P3/06 ,  A61P3/00

CPC分类号： A61K31/7056 ,  A61K31/706 ,  A61K45/06 ,  C07H19/04 ,  A61K2300/00

摘要： A compound having SGLT1 and/or SGLT2 inhibitory activity which is usable as an agent for the prevention or treatment of diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications, obesity, etc. It is a 1-(β-D-glycopyranosyl)-3-substituted nitrogen-containing heterocyclic compound represented by the general formula (I), a prodrug, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof; an SGLT inhibitor containing the same; a pharmaceutical composition containing the same and a medicinal use thereof. In the formula, ring A represents optionally substituted aryl or heteroaryl; Q1 to Q5 independently represent a carbon atom having a hydrogen atom or substituent bonded thereto or a nitrogen atom; E represents a single bond, alkylene, —O—, —S— or —NH—; and R represents methyl, ethyl, fluoromethyl or hydroxymethyl.

摘要翻译： 具有SGLT1和/或SGLT2抑制活性的化合物，其可用作预防或治疗糖尿病，餐后高血糖症，葡萄糖耐量降低，糖尿病并发症，肥胖症等的药物。它是1-（β-D-糖吡喃糖基） 由通式（I）表示的3-取代的含氮杂环化合物，其前体药物或其药学上可接受的盐，或其水合物或溶剂化物; 含有其的SGLT抑制剂; 含有该组合物的药物组合物及其药物用途。 在该式中，环A表示任选取代的芳基或杂芳基; Q 1至Q 5独立地表示具有与其键合的氢原子或取代基的碳原子或氮原子; E表示单键，亚烷基，-O - ， - S-或-NH-; R代表甲基，乙基，氟甲基或羟甲基。

公开(公告)号：US07749972B2

公开(公告)日：2010-07-06

申请号：US11816056

申请日：2006-02-14

申请人： Nobuhiko Fushimi ,  Shigeru Yonekubo ,  Kohsuke Ohno

发明人： Nobuhiko Fushimi ,  Shigeru Yonekubo ,  Kohsuke Ohno

IPC分类号： A61K31/70 ,  A01N43/04 ,  C07H17/02

CPC分类号： A61K45/06 ,  A61K31/7056 ,  C07H17/02

摘要： The present invention provides a compound having an SGLT1 and/or SGLT2 inhibitory activity which is usable as an agent for the prevention or treatment of diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications, obesity or the like.It is a 1-substituted-7-(β-D-glycopyranosyloxy)(aza)-indole compound represented by the general formula (I), a prodrug thereof, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof: wherein R1 represents a halogen atom or the like; n represents j an integer number from 0 to 3; R2 represents a hydrogen atom or the like; X represents a carbon atom which a hydrogen atom or the like binds to, or a nitrogen atom; Q represents an alkylene group or an alkenylene group each of which may have an oxygen atom or a sulfur atom in the chain; and A represents an aryl or heteroaryl group which may have a substituent.

摘要翻译： 本发明提供具有SGLT1和/或SGLT2抑制活性的化合物，其可用作预防或治疗糖尿病，餐后高血糖症，葡萄糖耐量降低，糖尿病并发症，肥胖症等。 它是由通式（I）表示的1-取代-7 - （＆bgr-D-吡喃葡萄糖基氧基）（氮杂） - 吲哚化合物，其前体药物或其药学上可接受的盐，或其水合物或溶剂化物： 其中R1表示卤素原子等; n表示j为0〜3的整数; R2表示氢原子等; X表示与氢原子等结合的碳原子或氮原子; Q表示可以在链中具有氧原子或硫原子的亚烷基或亚烯基; A表示可以具有取代基的芳基或杂芳基。

公开(公告)号：US20100112090A1

公开(公告)日：2010-05-06

申请号：US12596313

申请日：2008-04-16

申请人： Shigeru Yonekubo ,  Takashi Miyagi ,  Kohsuke Ohno ,  Mikie Kambara ,  Nobuhiko Fushimi

发明人： Shigeru Yonekubo ,  Takashi Miyagi ,  Kohsuke Ohno ,  Mikie Kambara ,  Nobuhiko Fushimi

IPC分类号： A61K31/437 ,  C07D471/04 ,  C07D473/28 ,  C07D473/00 ,  C07D495/04 ,  C07D473/04 ,  A61K31/522 ,  A61K31/52 ,  A61K38/09 ,  A61K31/664 ,  A61K31/704 ,  A61K38/14 ,  A61K31/56 ,  A61K31/496 ,  A61P13/08 ,  A61P15/18 ,  A61P35/00 ,  A61P15/00 ,  A61P5/00 ,  A61P37/00 ,  A61P25/28 ,  A61P15/08 ,  A61K31/55 ,  A61K31/4985 ,  A61K33/24

CPC分类号： C07D471/04 ,  A61K31/437 ,  A61K31/52 ,  C07D473/00 ,  C07D473/04 ,  C07D473/30 ,  C07D473/36 ,  C07D473/40 ,  C07D487/04

摘要： [Purpose] The present invention provides compounds useful as agents for the prevention or treatment of a sex hormone-dependent disease or the like.[Solution] The present invention provides nitrogen-containing fused ring derivatives represented by the following general formula (I) which has a GnRH antagonistic activity, prodrugs, salts, pharmaceutical compositions containing the same, medicinal uses thereof and the like. In the formula (I), rings A and B are independently aryl or heteroaryl; RA and RB are independently halogen, cyano, alkyl, alkylsulfonyl, —OW1, —SW1, —COW2, —NW3W4, —SO2NW3W4, aryl, etc.; RC is H or alkyl; E is oxygen atom, etc.; U is single bond or alkylene; and X is Y, —CO—Y, —SO2—Y, —S-(alkylene)-Y, —O-(alkylene)-Y, —SO2-(alkylene)-Y, etc.; Y is Z or amino, etc.; and Z is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, etc.

摘要翻译： [目的]本发明提供可用作预防或治疗性激素依赖性疾病等的药剂的化合物。 [溶液]本发明提供了具有GnRH拮抗活性的下述通式（I）表示的含氮稠环衍生物，前药，盐，含有它们的药物组合物，其药用用途等。 在式（I）中，环A和B独立地为芳基或杂芳基; RA和RB独立地是卤素，氰基，烷基，烷基磺酰基，-OW1，-SW1，-COW2，-NW3W4，-SO2NW3W4，芳基等; RC是H或烷基; E是氧原子等; U是单键或亚烷基; 并且X是Y，-CO-Y，-SO 2 -Y，-S-（亚烷基）-Y，-O-（亚烷基）-Y，-SO 2 - （亚烷基）-Y等; Y是Z或氨基等; Z是环烷基，杂环烷基，芳基，杂芳基等。

公开(公告)号：US20100130514A1

公开(公告)日：2010-05-27

申请号：US12596301

申请日：2008-04-16

申请人： Takashi Miyagi ,  Shigeru Yonekubo ,  Kohsuke Ohno ,  Mikie Kambara ,  Nobuhiko Fushimi

发明人： Takashi Miyagi ,  Shigeru Yonekubo ,  Kohsuke Ohno ,  Mikie Kambara ,  Nobuhiko Fushimi

IPC分类号： A61K31/519 ,  C07D495/04

CPC分类号： C07D495/04 ,  A61K31/519 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention provides compounds useful as agents for the prevention or treatment of a sex hormone-dependent disease or the like. That is, the present invention provides fused heterocyclic derivatives represented by the following general formula (I), pharmaceutical compositions containing the same, medicinal uses thereof and the like. In the formula (I), rings A is 5-membered cyclic unsaturated hydrocarbon or 5-membered heteroaryl; RA is halogen, alkyl, alkenyl, alkynyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl, etc.; ring B is aryl or heteroaryl; RB is halogen, alkyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl, etc.; E1 and E2 are oxygen atom, etc.; U is single bond or alkylene; X is a group represented by Y, —O-(alkylene)-Y or —O—Z (in which Y is Z or amino substituted by Z, etc.; Z is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, etc.

摘要翻译： 本发明提供了可用作预防或治疗性激素依赖性疾病等的试剂的化合物。 也就是说，本发明提供由以下通式（I）表示的稠合杂环衍生物，含有它们的药物组合物，其药用用途等。 在式（I）中，环A是5元环状不饱和烃或5元杂芳基; RA是卤素，烷基，烯基，炔基，羧基，烷氧基，氨基甲酰基，烷基氨基甲酰基等; 环B是芳基或杂芳基; RB是卤素，烷基，羧基，烷氧基，氨基甲酰基，烷基氨基甲酰基等; E1和E2是氧原子等; U是单键或亚烷基; X是由Y，-O-（亚烷基）-Y或-O-Z（其中Y是Z或被Z取代的氨基等）表示的基团; Z是环烷基，杂环烷基，芳基，杂芳基等。

公开(公告)号：US08217069B2

公开(公告)日：2012-07-10

申请号：US12596313

申请日：2008-04-16

申请人： Shigeru Yonekubo ,  Takashi Miyagi ,  Kohsuke Ohno ,  Mikie Kambara ,  Nobuhiko Fushimi

发明人： Shigeru Yonekubo ,  Takashi Miyagi ,  Kohsuke Ohno ,  Mikie Kambara ,  Nobuhiko Fushimi

IPC分类号： A61K31/415 ,  C07D233/00

CPC分类号： C07D471/04 ,  A61K31/437 ,  A61K31/52 ,  C07D473/00 ,  C07D473/04 ,  C07D473/30 ,  C07D473/36 ,  C07D473/40 ,  C07D487/04

摘要： [Purpose] The present invention provides compounds useful as agents for the prevention or treatment of a sex hormone-dependent disease or the like.[Solution] The present invention provides nitrogen-containing fused ring derivatives represented by the following general formula (I) which has a GnRH antagonistic activity, prodrugs, salts, pharmaceutical compositions containing the same, medicinal uses thereof and the like. In the formula (I), rings A and B are independently aryl or heteroaryl; RA and RB are independently halogen, cyano, alkyl, alkylsulfonyl, —OW1, —SW1, —COW2, —NW3W4, —SO2NW3W4, aryl, etc.; RC is H or alkyl; E is oxygen atom, etc.; U is single bond or alkylene; and X is Y, —CO—Y, —SO2—Y, —S-(alkylene)-Y, —O-(alkylene)-Y, —SO2-(alkylene)-Y, etc.; Y is Z or amino, etc.; and Z is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, etc.

摘要翻译： [目的]本发明提供可用作预防或治疗性激素依赖性疾病等的药剂的化合物。 [溶液]本发明提供了具有GnRH拮抗活性的下述通式（I）表示的含氮稠环衍生物，前药，盐，含有它们的药物组合物，其药用用途等。 在式（I）中，环A和B独立地为芳基或杂芳基; RA和RB独立地是卤素，氰基，烷基，烷基磺酰基，-OW1，-SW1，-COW2，-NW3W4，-SO2NW3W4，芳基等; RC是H或烷基; E是氧原子等; U是单键或亚烷基; 并且X是Y，-CO-Y，-SO 2 -Y，-S-（亚烷基）-Y，-O-（亚烷基）-Y，-SO 2 - （亚烷基）-Y等; Y是Z或氨基等; Z是环烷基，杂环烷基，芳基，杂芳基等。

公开(公告)号：US20100081674A1

公开(公告)日：2010-04-01

申请号：US12595931

申请日：2008-04-16

申请人： Kohsuke Ohno ,  Noboru Kamada

发明人： Kohsuke Ohno ,  Noboru Kamada

IPC分类号： A61K31/519 ,  C07D495/04

CPC分类号： C07D495/04

摘要： The present invention provides compounds useful as agents for the prevention or treatment of a sex hormone-dependent disease or the like. That is, the present invention provides fused heterocyclic derivatives represented by the following general formula (I) which has a GnRH antagonistic activity, pharmaceutical compositions containing the same, medicinal uses thereof and the like. In the formula (I), rings A is 5-membered cyclic unsaturated hydrocarbon or 5-membered heteroaryl; RA is halogen, alkyl, alkenyl, alkynyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl, etc.; ring B is aryl or heteroaryl; RB is halogen, alkyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl, etc.; E1 and E2 are oxygen atom, etc.; Q is hydrogen atom, alkyl, alkylsulfonyl, acyl, etc.; X is -(alkylene)-Z, —CO—Y, —SO2—Y, etc. (in which Y is Z or amino, etc.; Z is cycloalkyl, heterocycloalkyl, aryl, heteroaryl, etc.

摘要翻译： 本发明提供了可用作预防或治疗性激素依赖性疾病等的试剂的化合物。 也就是说，本发明提供具有GnRH拮抗活性的由以下通式（I）表示的稠合杂环衍生物，含有它们的药物组合物，其药用用途等。 在式（I）中，环A是5元环状不饱和烃或5元杂芳基; RA是卤素，烷基，烯基，炔基，羧基，烷氧基，氨基甲酰基，烷基氨基甲酰基等; 环B是芳基或杂芳基; RB是卤素，烷基，羧基，烷氧基，氨基甲酰基，烷基氨基甲酰基等; E1和E2是氧原子等; Q是氢原子，烷基，烷基磺酰基，酰基等; X是 - （亚烷基）-Z，-CO-Y，-SO2-Y等（其中Y是Z或氨基等; Z是环烷基，杂环烷基，芳基，杂芳基等）

公开(公告)号：US20090325900A1

公开(公告)日：2009-12-31

申请号：US12089674

申请日：2006-10-17

申请人： Kohsuke Ohno ,  Takashi Miyagi ,  Tomonaga Ozawa ,  Nobuhiko Fushimi

发明人： Kohsuke Ohno ,  Takashi Miyagi ,  Tomonaga Ozawa ,  Nobuhiko Fushimi

IPC分类号： A61K31/695 ,  C07D215/58 ,  C07D211/72 ,  C07D311/02 ,  A61K31/47 ,  A61K31/44 ,  C07D223/16 ,  A61K31/55 ,  A61P5/24

CPC分类号： C07D495/04

摘要： The present invention provides a compound useful as an agent for the prevention or treatment of a sex hormone-dependent disease or the like. That is, the present invention provides a fused heterocyclic derivative represented by the following general formula (I), a pharmaceutical composition containing the same, a medicinal use thereof and the like. In the formula (I), ring A represents 5-membered cyclic unsaturated hydrocarbon or 5-membered heteroaryl; RA represents halogen, alkyl, alkenyl, alkynyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl or the like; ring B represents aryl or heteroaryl; RB represents halogen, alkyl, carboxy, alkoxy, carbamoyl, alkylcarbamoyl or the like; E1 and E2 represent an oxygen atom or the like; U represents a single bond or alkylene; X represents a group represented by Y, —SO2—Y, —O— (alkylene)-Y, —O-Z in which Y represents Z, amino or the like; Z represents cycloalkyl, heterocycloalkyl, aryl, heteroaryl or the like; or the like.

摘要翻译： 本发明提供了可用作预防或治疗性激素依赖性疾病等的药剂的化合物。 也就是说，本发明提供由以下通式（I）表示的稠合杂环衍生物，含有该杂环衍生物的药物组合物，其医药用途等。 在式（I）中，环A表示5元环状不饱和烃或5元杂芳基; 烷基，烯基，炔基，羧基，烷氧基，氨基甲酰基，烷基氨基甲酰基等; 环B表示芳基或杂芳基; RB代表卤素，烷基，羧基，烷氧基，氨基甲酰基，烷基氨基甲酰基等; E1和E2表示氧原子等; U表示单键或亚烷基; X表示Y表示的基团，-SO 2 -Y，-O-（亚烷基）-Y，-O-Z，Y表示Z，氨基等; Z表示环烷基，杂环烷基，芳基，杂芳基等; 或类似物。