公开(公告)号：US20150218151A1

公开(公告)日：2015-08-06

申请号：US14427865

申请日：2013-09-25

Applicant: KOWA COMPANY, LTD.

Inventor： Takahisa Ogamino ,  Shin Tanikawa ,  Yoshiharu Miyake ,  Shinsuke Itoh ,  Yoshikazu Sawada

IPC: C07D417/14 ,  C07D403/12 ,  C07D401/12 ,  C07D417/12

CPC classification number: C07D417/14 ,  A61K31/4155 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/497 ,  C07D401/12 ,  C07D403/12 ,  C07D417/12

Abstract: The present invention is to create a compound that selectively activates glucokinase in the liver, and in particular, to provide an agent for treating and preventing diabetes and impaired glucose tolerance, wherein the agent has a low hypoglycemia risk.A compound represented by the formula (1) as shown below, or a salt thereof, or a solvate of the compound or the salt:[wherein, in the following formula (1), ring A represents a thiazolyl group, a pyridyl group, a pyrazyl group, or a pyrazolyl group; L represents —(CO)—, —(CS)—, or —SO2—; and R1 represents a C1-6 alkyl group, a hydroxy C1-6 alkyl group, a C1-6 alkoxy group, an amino group, a C1-6 alkylamino group, a hydroxyamino group, an N—C1-6 alkylcarbamoyl group, or a group represented by the formula (2) as shown below, wherein R3 represents a C1-6 alkyl group; and R2 represents a hydrogen atom, a halogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, or a carboxyl group].

Abstract translation: 本发明是产生选择性地激活肝脏中的葡萄糖激酶的化合物，特别是提供治疗和预防糖尿病和葡萄糖耐量降低的药剂，其中该药物具有低的低血糖风险。 由下式（1）表示的化合物或其盐或化合物或其盐的溶剂化物：[其中，在下式（1）中，环A表示噻唑基，吡啶基， 吡唑基或吡唑基; L代表 - （CO） - ， - （CS） - 或-SO2-; 和R 1表示C 1-6烷基，羟基C 1-6烷基，C 1-6烷氧基，氨基，C 1-6烷基氨基，羟基氨基，N-C 1-6烷基氨基甲酰基或 由下式（2）表示的基团，其中R 3表示C 1-6烷基; R 2表示氢原子，卤素原子，C 1-6烷基，C 1-6烷氧基或羧基。

公开(公告)号：US09242978B2

公开(公告)日：2016-01-26

申请号：US14427865

申请日：2013-09-25

Applicant: KOWA COMPANY, LTD.

Inventor： Takahisa Ogamino ,  Shin Tanikawa ,  Yoshiharu Miyake ,  Shinsuke Itoh ,  Yoshikazu Sawada

IPC: C07D401/12 ,  C07D403/12 ,  C07D417/12 ,  A61K31/4155 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/497 ,  C07D417/14

CPC classification number: C07D417/14 ,  A61K31/4155 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/497 ,  C07D401/12 ,  C07D403/12 ,  C07D417/12

Abstract: The present invention is to create a compound that selectively activates glucokinase in the liver, and in particular, to provide an agent for treating and preventing diabetes and impaired glucose tolerance, wherein the agent has a low hypoglycemia risk. A compound represented by the formula (1) as shown below, or a salt thereof, or a solvate of the compound or the salt:wherein, in the following formula (1), ring A represents a thiazolyl group, a pyridyl group, a pyrazyl group, or a pyrazolyl group; L represents —(CO)—, —(CS)—, or —SO2—; and R1 represents a C1-6 alkyl group, a hydroxy C1-6 alkyl group, a C1-6 alkoxy group, an amino group, a C1-6 alkylamino group, a hydroxyamino group, an N—C1-6 alkylcarbamoyl group, or a group represented by the formula (2) as shown below, wherein R3 represents a C1-6 alkyl group; and R2 represents a hydrogen atom, a halogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, or a carboxyl group. The formulas are shown below:

Abstract translation: 本发明是产生选择性地激活肝脏中的葡萄糖激酶的化合物，特别是提供治疗和预防糖尿病和葡萄糖耐量降低的药剂，其中该药物具有低的低血糖风险。 由下式（1）表示的化合物或其盐或化合物或其盐的溶剂合物：其中，在下式（1）中，环A表示噻唑基，吡啶基， 吡唑基或吡唑基; L代表 - （CO） - ， - （CS） - 或-SO2-; 和R 1表示C 1-6烷基，羟基C 1-6烷基，C 1-6烷氧基，氨基，C 1-6烷基氨基，羟基氨基，N-C 1-6烷基氨基甲酰基或 由下式（2）表示的基团，其中R 3表示C 1-6烷基; R 2表示氢原子，卤素原子，C 1-6烷基，C 1-6烷氧基或羧基。 公式如下所示：

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]