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：US09682913B2

公开(公告)日：2017-06-20

申请号：US14780625

申请日：2014-03-28

Applicant: KOWA COMPANY, LTD.

Inventor： Yukiyoshi Yamazaki

IPC: C07B57/00 ,  C07C51/41 ,  A61K31/423 ,  C07D263/58 ,  C07C67/08

CPC classification number: C07C51/412 ,  A61K31/423 ,  C07B57/00 ,  C07C67/08 ,  C07D263/58 ,  C07C51/487 ,  C07C59/01

Abstract: To provide a method for improving optical purity of an optically active 2-hydroxycarboxylic acid or a derivative thereof, which is useful as a raw material in the manufacture of medicines, agrochemicais, and industrial products. The method of the invention for improving purity of a hydroxycarboxylic acid of the following formula (1a) or (1b) or a derivative thereof includes the steps of reacting the hydroxycarboxylic acid of the following formula (1a) or (1b) with at least one optically inactive base selected from the group consisting of an alkali metal, alkoxide and a secondary amine in the presence of a solvent and, subsequently, performing recrystallization, to thereby form a hydroxycarboxylic acid salt of the following formula (IIIa) or (IIIb): wherein R1 represents a C1-8 alkyl group, and R2 represents an alkali metal or a secondary amine.