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：US20140330022A1

公开(公告)日：2014-11-06

申请号：US14370144

申请日：2013-01-04

Applicant: KOWA COMPANY, LTD.

Inventor： Hideo Yoshida ,  Shinsuke Itoh

IPC: A61K31/4704

CPC classification number: A61K31/4704 ,  C07D215/22

Abstract: Provided is compound for improving blood flow at sites of impaired circulation in the extremities, through promoting development of collateral blood circulation without angiogenesis; also provided is a therapeutic agent for sensitivity to cold or cold sensation, in which the active ingredient is a compound for improving blood flow at sites of impaired circulation in the extremities. A collateral blood flow development promoter, in which the active ingredient is (−)-6-[3-[3-cyclopropyl-3-[(1R,2R)-2-hydroxycyclohexyl]ureido]propoxy]-2(1H)-quinolinone or a salt thereof, or a solvate thereof.

Abstract translation: 提供了通过促进血管生成的侧支血液循环的发展来改善四肢受损循环部位的血流量的化合物; 还提供了对冷或感觉敏感的治疗剂，其中活性成分是用于改善四肢中循环受损部位的血液流动的化合物。 其中活性成分为（ - ） - 6- [3- [3-环丙基-3 - [（1R，2R）-2-羟基环己基]脲基]丙氧基] -2（1H） - 喹啉酮或其盐，或其溶剂合物。

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]