公开(公告)号：US09045423B2

公开(公告)日：2015-06-02

申请号：US14274805

申请日：2014-05-12

Applicant: KOWA COMPANY, LTD.

Inventor： Masanori Ashikawa ,  Junya Tagashira ,  Akiyasu Koketsu ,  Toshiharu Morimoto ,  Takahiro Kitamura ,  Syunji Takemura ,  Gen Watanabe ,  Tatsuaki Nishiyama ,  Satoshi Goda ,  Masaki Yamabi ,  Takeshi Doi ,  Hiroyuki Ishiwata

IPC: A01N57/26 ,  A61K31/675 ,  C07D215/42 ,  A61K31/47 ,  A61K31/4706 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/69 ,  C07D215/233 ,  C07D215/44 ,  C07D215/46 ,  C07D215/48 ,  C07D401/04 ,  C07D401/12 ,  C07D413/04 ,  C07D413/12 ,  C07D417/12 ,  C07D405/12

CPC classification number: C07D215/42 ,  A61K31/47 ,  A61K31/4706 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/69 ,  C07D215/233 ,  C07D215/44 ,  C07D215/46 ,  C07D215/48 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D413/04 ,  C07D413/12 ,  C07D417/12

Abstract: Disclosed is a compound which has a low molecular weight and has an activity of enhancing the production of EPO and/or an activity of enhancing the production of hemoglobin. Specifically disclosed is and EPO production enhancer and/or a hemoglobin production enhancer comprising a 1-acyl-4-(substituted oxy, substituted amino, or substituted thio)-1,2,3,4-tetrahydroquinoline derivative, more specifically a tetrahydroquinoline compound represented by general formula (1) [wherein R1, R2, R2′, R3 and R3′ independently represent a hydrogen atom, a C1-6 alkyl group, or the like; R4, R5, R6, R7, R8, R9 and R10 independently represent a hydrogen atom, a halogen atom, a C1-6 alkyl group, or the like; A represents N—R11, a sulfur atom, or an oxygen atom; R11 represents a hydrogen atom, a C1-6 alkyl group, or the like; B represents a C6-14 aryl group, or a 5- to 10-membered heterocyclic group; and n represents an integer of 0 or 1], a salt of the tetrahydroquinoline compound, or a solvate of the tetrahydroquinoline compound or the salt.

Abstract translation: 公开了具有低分子量且具有增强EPO产生活性和/或提高血红蛋白生成活性的化合物。 具体公开的是EPO生产增强剂和/或包含1-酰基-4-（取代的氧基，取代的氨基或取代的硫代）-1,2,3,4-四氢喹啉衍生物，更具体地是四氢喹啉化合物的血红蛋白生成增强剂 由通式（1）表示[其中R1，R2，R2'，R3和R3'独立地表示氢原子，C1-6烷基等; R 4，R 5，R 6，R 7，R 8，R 9和R 10独立地表示氢原子，卤素原子，C 1-6烷基等; A表示N-R11，硫原子或氧原子; R 11表示氢原子，C 1-6烷基等; B表示C 6-14芳基或5至10元杂环基; n表示0或1的整数]，四氢喹啉化合物的盐或四氢喹啉化合物或其盐的溶剂合物。

公开(公告)号：US08921576B2

公开(公告)日：2014-12-30

申请号：US14351914

申请日：2012-10-18

Applicant: Kowa Company, Ltd.

Inventor： Takahisa Ogamino ,  Yukiyoshi Yamazaki ,  Shin Tanikawa ,  Ayumu Okuda ,  Tomoaki Fukuda ,  Okihisa Tokuda ,  Yoshiharu Miyake ,  Shinsuke Itoh ,  Hiroyuki Ishiwata

IPC: C07D487/10 ,  C07D519/00

CPC classification number: C07D487/10 ,  C07D519/00

Abstract: The present invention provides a novel compound represented by a general formula (1) as shown below, which has a glucokinase-activating action in the liver and pancreatic β-cells and which is useful as an agent for preventing and/or treating diseases caused by hyperglycemia, such as diabetes.A spiroindoline compound represented by the general formula (1), or a salt thereof, or a solvate of the compound or the salt: [wherein ring A represents a nitrogen-containing 5-10 membered heteroaryl group; R1 and R2, which are the same or different, each represent a hydrogen atom, a halogen atom, a halo C1-6 alkyl group, a C6-10 aryl group, a cyano group, a C1-6 alkyl group optionally having a substituent, a C2-6 alkenyl group optionally having a substituent, etc.; R3 represents a hydrogen atom, a C1-6 alkyl group optionally having a substituent, etc.; and R4 represents a hydrogen atom, a halogen atom, a C1-6 alkyl group optionally having a substituent, etc.]

Abstract translation: 本发明提供如下所示的由通式（1）表示的新化合物，其在肝脏和胰腺细胞中具有葡萄糖激酶活化作用，并且其可用作预防和/或治疗疾病引起的药物 通过高血糖症，如糖尿病。 由通式（1）表示的螺二氢吲哚化合物或其盐或化合物或其盐的溶剂合物：[其中环A表示含氮5-10元杂芳基; R 1和R 2相同或不同，各自表示氢原子，卤素原子，卤代C 1-6烷基，C 6-10芳基，氰基，任选具有取代基的C 1-6烷基 任选具有取代基的C 2-6烯基等; R3表示氢原子，任选具有取代基的C1-6烷基等; R4代表氢原子，卤原子，任选具有取代基的C1-6烷基等]

公开(公告)号：US20140309207A1

公开(公告)日：2014-10-16

申请号：US14351914

申请日：2012-10-18

Applicant: KOWA COMPANY, LTD.

Inventor： Takahisa Ogamino ,  Yukiyoshi Yamazaki ,  Shin Tanikawa ,  Ayumu Okuda ,  Tomoaki Fukuda ,  Okihisa Tokuda ,  Yoshiharu Miyake ,  Shinsuke Itoh ,  Hiroyuki Ishiwata

IPC: C07D487/10 ,  C07D519/00

CPC classification number: C07D487/10 ,  C07D519/00

Abstract: The present invention provides a novel compound represented by a general formula (1) as shown below, which has a glucokinase-activating action in the liver and pancreatic β-cells and which is useful as an agent for preventing and/or treating diseases caused by hyperglycemia, such as diabetes.A spiroindoline compound represented by the general formula (1), or a salt thereof, or a solvate of the compound or the salt: [wherein ring A represents a nitrogen-containing 5-10 membered heteroaryl group; R1 and R2, which are the same or different, each represent a hydrogen atom, a halogen atom, a halo C1-6 alkyl group, a C6-10 aryl group, a cyano group, a C1-6 alkyl group optionally having a substituent, a C2-6 alkenyl group optionally having a substituent, etc.; R3 represents a hydrogen atom, a C1-6 alkyl group optionally having a substituent, etc.; and R4 represents a hydrogen atom, a halogen atom, a C1-6 alkyl group optionally having a substituent, etc.]

Abstract translation: 本发明提供如下所示的由通式（1）表示的新化合物，其在肝脏和胰腺细胞中具有葡萄糖激酶活化作用，并且其可用作预防和/或治疗疾病引起的药物 通过高血糖症，如糖尿病。 由通式（1）表示的螺二氢吲哚化合物或其盐或化合物或其盐的溶剂合物：[其中环A表示含氮5-10元杂芳基; R 1和R 2相同或不同，各自表示氢原子，卤素原子，卤代C 1-6烷基，C 6-10芳基，氰基，任选具有取代基的C 1-6烷基 任选具有取代基的C 2-6烯基等; R3表示氢原子，任选具有取代基的C1-6烷基等; R4代表氢原子，卤原子，任选具有取代基的C1-6烷基等]

公开(公告)号：US20140249144A1

公开(公告)日：2014-09-04

申请号：US14274805

申请日：2014-05-12

Applicant: KOWA COMPANY, LTD.

Inventor： Masanori Ashikawa ,  Junya Tagashira ,  Akiyasu Koketsu ,  Toshiharu Morimoto ,  Takahiro Kitamura ,  Syunji Takemura ,  Gen Watanabe ,  Tatsuaki Nishiyama ,  Satoshi Goda ,  Masaki Yamabi ,  Takeshi Doi ,  Hiroyuki Ishiwata

IPC: C07D417/12 ,  C07D401/12 ,  C07D401/04 ,  C07D405/12 ,  C07D413/04 ,  C07D215/42 ,  C07D413/12

CPC classification number: C07D215/42 ,  A61K31/47 ,  A61K31/4706 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/69 ,  C07D215/233 ,  C07D215/44 ,  C07D215/46 ,  C07D215/48 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D413/04 ,  C07D413/12 ,  C07D417/12

Abstract: Disclosed is a compound which has a low molecular weight and has an activity of enhancing the production of EPO and/or an activity of enhancing the production of hemoglobin. Specifically disclosed is and EPO production enhancer and/or a hemoglobin production enhancer comprising a 1-acyl-4-(substituted oxy, substituted amino, or substituted thio)-1,2,3,4-tetrahydroquinoline derivative, more specifically a tetrahydroquinoline compound represented by general formula (1) [wherein R1, R2, R2′, R3 and R3′ independently represent a hydrogen atom, a C1-6 alkyl group, or the like; R4, R5, R6, R7, R8, R9 and R10 independently represent a hydrogen atom, a halogen atom, a C1-6 alkyl group, or the like; A represents N—R11, a sulfur atom, or an oxygen atom; R11 represents a hydrogen atom, a C1-6 alkyl group, or the like; B represents a C6-14 aryl group, or a 5- to 10-membered heterocyclic group; and n represents an integer of 0 or 1], a salt of the tetrahydroquinoline compound, or a solvate of the tetrahydroquinoline compound or the salt.

Abstract translation: 公开了具有低分子量且具有增强EPO产生活性和/或提高血红蛋白生成活性的化合物。 具体公开的是EPO生产增强剂和/或包含1-酰基-4-（取代的氧基，取代的氨基或取代的硫代）-1,2,3,4-四氢喹啉衍生物，更具体地是四氢喹啉化合物的血红蛋白生成增强剂 由通式（1）表示[其中R1，R2，R2'，R3和R3'独立地表示氢原子，C1-6烷基等; R 4，R 5，R 6，R 7，R 8，R 9和R 10独立地表示氢原子，卤素原子，C 1-6烷基等; A表示N-R11，硫原子或氧原子; R 11表示氢原子，C 1-6烷基等; B表示C 6-14芳基或5至10元杂环基; n表示0或1的整数]，四氢喹啉化合物的盐或四氢喹啉化合物或其盐的溶剂合物。

公开(公告)号：US20130172345A1

公开(公告)日：2013-07-04

申请号：US13770175

申请日：2013-02-19

Applicant: KOWA COMPANY, LTD.

Inventor： Masanori Ashikawa ,  Junya Tagashira ,  Akiyasu Koketsu ,  Toshiharu Morimoto ,  Tatsuaki Nishiyama ,  Satoshi Goda ,  Masaki Yamabi ,  Takeshi Doi ,  Hiroyuki Ishiwata

IPC: C07D215/48 ,  C07D413/12

CPC classification number: C07D215/48 ,  A61K31/47 ,  A61K31/4706 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/5377 ,  C07D215/22 ,  C07D215/44 ,  C07D413/04 ,  C07D413/12

Abstract: Disclosed is a low-molecular-weight compound having an EPO production-promoting activity and/or a hemoglobin expression-enhancing activity. Specifically disclosed is an EPO production promoter and/or a hemoglobin expression enhancer comprising a 1-acyl-4-(phenoxy, benzyloxy or phenylamino)-1,2,3,4-tetrahydroquinoline derivative, more specifically a tetrahydroquinoline compound represented by the general formula (1); [wherein R1, R2, R2′, R3 and R3′ independently represent a hydrogen atom, a C1-6 alkyl group, or the like; R4, R5, R6, R7, R8, R9 and R16 independently represent a hydrogen atom, a halogen atom, a C1-6 alkyl group, or the like; A represents N—R11 or an oxygen atom; R11 represents a hydrogen atom, a C1-6 alkyl group, or the like; and n represents an integer of 0 or 1], a salt of the tetrahydroquinoline compound, or a solvate of the tetrahydroquinoline compound or the salt.

Abstract translation: 公开了具有EPO生产促进活性和/或血红蛋白表达增强活性的低分子量化合物。 具体公开的是EPO生产促进剂和/或血红蛋白表达增强剂，其包含1-酰基-4-（苯氧基，苄氧基或苯基氨基）-1,2,3,4-四氢喹啉衍生物，更具体地是由通式 公式1）; [其中R1，R2，R2'，R3和R3'独立地表示氢原子，C1-6烷基等; R4，R5，R6，R7，R8，R9和R16独立地表示氢原子，卤素原子，C1-6烷基等; A表示N-R11或氧原子; R 11表示氢原子，C 1-6烷基等; n表示0或1的整数]，四氢喹啉化合物的盐或四氢喹啉化合物或其盐的溶剂合物。