公开(公告)号：US08232308B2

公开(公告)日：2012-07-31

申请号：US12925367

申请日：2010-10-20

申请人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

发明人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

IPC分类号： A01N43/56 ,  A61K31/40 ,  C07D231/00 ,  C07D233/56

CPC分类号： C07D231/56 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04

摘要： A method for treating a disease in which Rho kinase is involved. The method is carried out by administering to a patient in need thereof a pharmaceutically effective amount of a compound of the following formula or a pharmaceutically acceptable salt thereof: wherein the ring X is a benzene ring or a pyridine ring; R1 and R2 are hydrogen or alkyl or together form a cycloalkene ring; R3 is hydrogen, substituted alkyl, unsubstituted alkenyl, carboxyl or an ester or an amide thereof, amino or a cyano; R4 is hydrogen, hydroxyl, substituted or unsubstituted alkoxy, unsubstituted alkenyloxy, unsubstituted cycloalkyloxy substituted or unsubstituted alkyl, unsubstituted alkenyl, unsubstituted cycloalkyl, amino, substituted or unsubstituted alkylamino, nitro, cyano or a monocyclic heterocycle; and R5 is a halogen atom or a hydrogen atom.

摘要翻译： 一种治疗涉及Rho激酶的疾病的方法。 该方法通过向有需要的患者施用药学有效量的下式化合物或其药学上可接受的盐进行：其中环X是苯环或吡啶环; R1和R2是氢或烷基或一起形成环烯烃环; R 3是氢，取代的烷基，未取代的烯基，羧基或其酯或酰胺，氨基或氰基; R4是氢，羟基，取代或未取代的烷氧基，未取代的烯氧基，未取代的环烷基氧基取代或未取代的烷基，未取代的烯基，未取代的环烷基，氨基，取代或未取代的烷基氨基，硝基，氰基或单环杂环; R5为卤素原子或氢原子。

公开(公告)号：US20060052367A1

公开(公告)日：2006-03-09

申请号：US10535000

申请日：2003-11-17

申请人： Masakazu Hatano ,  Tadashi Nakajima ,  Takeshi Matsugi ,  Hideaki Hara

发明人： Masakazu Hatano ,  Tadashi Nakajima ,  Takeshi Matsugi ,  Hideaki Hara

IPC分类号： A61K31/551 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/4745

CPC分类号： A61K45/06 ,  A61K31/138 ,  A61K31/343 ,  A61K31/353 ,  A61K31/437 ,  A61K31/4409 ,  A61K31/4412 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/551 ,  Y10S514/913 ,  A61K2300/00

摘要： A subject of the present invention is to find utility of a combination of a Rho kinase inhibitor having a novel action and a β-blocker as a therapeutic agent for glaucoma. Actions of reducing intraocular pressure are complemented and/or enhanced each other by combining the Rho kinase inhibitor with the β-blocker. For the administration mode, each drug can be administered in combination or in mixture.

摘要翻译： 本发明的主题是发现具有新作用的Rho激酶抑制剂和β-阻断剂的组合作为青光眼治疗剂的用途。 通过组合Rho激酶抑制剂与β受体阻滞剂相互补充和/或相互增强降低眼内压的作用。 对于给药模式，每种药物可以组合或混合施用。

公开(公告)号：US07972612B2

公开(公告)日：2011-07-05

申请号：US10535000

申请日：2003-11-17

申请人： Masakazu Hatano ,  Tadashi Nakajima ,  Takeshi Matsugi ,  Hideaki Hara

发明人： Masakazu Hatano ,  Tadashi Nakajima ,  Takeshi Matsugi ,  Hideaki Hara

IPC分类号： A61K9/00 ,  A61K31/535 ,  A61K31/44

CPC分类号： A61K45/06 ,  A61K31/138 ,  A61K31/343 ,  A61K31/353 ,  A61K31/437 ,  A61K31/4409 ,  A61K31/4412 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/551 ,  Y10S514/913 ,  A61K2300/00

摘要： A subject of the present invention is to find utility of a combination of a Rho kinase inhibitor having a novel action and a β-blocker as a therapeutic agent for glaucoma. Actions of reducing intraocular pressure are complemented and/or enhanced each other by combining the Rho kinase inhibitor with the β-blocker. For the administration mode, each drug can be administered in combination or in mixture.

摘要翻译： 本发明的主题是发现具有新作用的Rho激酶抑制剂与抑制剂组合作为青光眼治疗剂的用途。 通过将Rho激酶抑制剂与抑制剂结合来补充和/或增强眼内压降低的作用。 对于给药模式，每种药物可以组合或混合施用。

公开(公告)号：US20110263638A1

公开(公告)日：2011-10-27

申请号：US13135295

申请日：2011-06-30

申请人： Masakazu Hatano ,  Tadashi Nakajima ,  Takeshi Matsugi ,  Hideaki Hara

发明人： Masakazu Hatano ,  Tadashi Nakajima ,  Takeshi Matsugi ,  Hideaki Hara

IPC分类号： A61K31/437 ,  A61P27/06

CPC分类号： A61K45/06 ,  A61K31/138 ,  A61K31/343 ,  A61K31/353 ,  A61K31/437 ,  A61K31/4409 ,  A61K31/4412 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/551 ,  Y10S514/913 ,  A61K2300/00

摘要： A therapeutic agent for glaucoma including a combination of pharmaceutically effective amounts of a Rho kinase inhibitor and a β-blocker, wherein the Rho kinase inhibitor is (R)-(+)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-4-(1-aminoethyl)benzamide and the β-blocker is befunolol, carteolol, nipradilol, betaxolol, levobunolol or metipranolol. A method of treating glaucoma including administering effective amounts of a Rho kinase inhibitor and a β-blocker to a patient, wherein the Rho kinase inhibitor is (R)-(+)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-4-(1-aminoethyl)benzamide and the β-blocker is befunolol, carteolol, nipradilol, betaxolol, levobunolol or metipranolol.

摘要翻译： 一种用于青光眼的治疗剂，其包括药学有效量的Rho激酶抑制剂和抑制剂的组合，其中所述Rho激酶抑制剂是（R） - （+） - N-（1H-吡咯并[2,3-b 吡啶-4-基）-4-（1-氨基乙基）苯甲酰胺，并且β-阻滞剂是非芬洛尔，卡替洛尔，阿普拉洛尔，倍他洛尔，左布洛尔或美替洛尔。 一种治疗青光眼的方法，包括向患者施用有效量的Rho激酶抑制剂和抑制剂，其中所述Rho激酶抑制剂是（R） - （+） - N-（1H-吡咯并[2,3-b 吡啶-4-基）-4-（1-氨基乙基）苯甲酰胺，并且β-阻滞剂是非芬洛尔，卡替洛尔，阿普拉洛尔，倍他洛尔，左布洛尔或美替洛尔。

公开(公告)号：US20070129404A1

公开(公告)日：2007-06-07

申请号：US10575645

申请日：2004-10-15

申请人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

发明人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

IPC分类号： A61K31/4439 ,  A61K31/416 ,  C07D403/02 ,  C07D231/56

CPC分类号： C07D231/56 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04

摘要： An object of the present invention is to create a novel indazole derivative useful as a drug and to find a novel pharmacological action of the derivative. The compound of the present invention is represented by the formula [I] and has an excellent Rho kinase inhibiting action. In the formula, a ring X is a benzene ring or a pyridine ring; R1 and R2 are H or alkyl; R3 and R4 are halogen, H, OH, alkoxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cycloalkenyloxy, aryloxy, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, carboxy, hydrocarbonyl, alkylcarbonyl, etc.; and R5 is halogen atom, H, OH, alkoxy, aryloxy, alkyl or aryl. Each group can be substituted.

摘要翻译： 本发明的目的是产生一种可用作药物的新型吲唑衍生物，并找到该衍生物的新药理作用。 本发明的化合物由式[I]表示，具有优异的Rho激酶抑制作用。 在该式中，环X为苯环或吡啶环; R 1和R 2均为H或烷基; R 3和R 4是卤素，H，OH，烷氧基，烯氧基，炔氧基，环烷氧基，环烯氧基，芳氧基，烷基，烯基，炔基，环烷基，环烯基，芳基， 羧基，烃基，烷基羰基等; R 5是卤素原子，H，OH，烷氧基，芳氧基，烷基或芳基。 每组可以替代。

公开(公告)号：US20110039891A1

公开(公告)日：2011-02-17

申请号：US12925367

申请日：2010-10-20

申请人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

发明人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

IPC分类号： A61K31/454 ,  A61K31/415 ,  A61K31/4439 ,  A61K31/422 ,  A61K31/42 ,  A61P27/02 ,  A61P27/06

CPC分类号： C07D231/56 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04

摘要： A method for treating a disease in which Rho kinase is involved. The method is carried out by administering to a patient in need thereof a pharmaceutically effective amount of a compound of the following formula or a pharmaceutically acceptable salt thereof: wherein the ring X is a benzene ring or a pyridine ring; R1 and R2 are hydrogen or alkyl or together form a cycloalkene ring; R3 is hydrogen, substituted alkyl, unsubstituted alkenyl, carboxyl or an ester or an amide thereof, amino or a cyano; R4 is hydrogen, hydroxyl, substituted or unsubstituted alkoxy, unsubstituted alkenyloxy, unsubstituted cycloalkyloxy substituted or unsubstituted alkyl, unsubstituted alkenyl, unsubstituted cycloalkyl, amino, substituted or unsubstituted alkylamino, nitro, cyano or a monocyclic heterocycle; and R5 is a halogen atom or a hydrogen atom.

摘要翻译： 一种治疗涉及Rho激酶的疾病的方法。 该方法通过向有需要的患者施用药学有效量的下式化合物或其药学上可接受的盐进行：其中环X是苯环或吡啶环; R1和R2是氢或烷基或一起形成环烯烃环; R 3是氢，取代的烷基，未取代的烯基，羧基或其酯或酰胺，氨基或氰基; R4是氢，羟基，取代或未取代的烷氧基，未取代的烯氧基，未取代的环烷基氧基取代或未取代的烷基，未取代的烯基，未取代的环烷基，氨基，取代或未取代的烷基氨基，硝基，氰基或单环杂环; R5为卤素原子或氢原子。

公开(公告)号：US07855222B2

公开(公告)日：2010-12-21

申请号：US12456652

申请日：2009-06-19

申请人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

发明人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

IPC分类号： A01N43/56 ,  A61K31/40 ,  C07D231/00 ,  C07D233/56

CPC分类号： C07D231/56 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04

摘要： A method for treating a disease in which Rho kinase is involved. The method is carried out by administering to a patient in need thereof a pharmaceutically effective amount of a compound of the following formula or a pharmaceutically acceptable salt thereof: wherein the ring X is a benzene ring or a pyridine ring; R1 and R2 are hydrogen or alkyl or together form a cycloalkene ring; R3 is hydrogen, substituted alkyl, unsubstituted alkenyl, carboxyl or an ester or an amide thereof, amino or a cyano; R4 is hydrogen, hydroxyl, substituted or unsubstituted alkoxy, unsubstituted alkenyloxy, unsubstituted cycloalkyloxy, substituted or unsubstituted alkyl, unsubstituted alkenyl, unsubstituted cycloalkyl, amino, substituted or unsubstituted alkylamino, nitro, cyano or a monocyclic heterocycle; and R5 is a halogen atom or a hydrogen atom.

摘要翻译： 一种治疗涉及Rho激酶的疾病的方法。 该方法通过向有需要的患者施用药学有效量的下式化合物或其药学上可接受的盐进行：其中环X是苯环或吡啶环; R1和R2是氢或烷基或一起形成环烯烃环; R 3是氢，取代的烷基，未取代的烯基，羧基或其酯或酰胺，氨基或氰基; R4是氢，羟基，取代或未取代的烷氧基，未取代的烯氧基，未取代的环烷基氧基，取代或未取代的烷基，未取代的烯基，未被取代的环烷基，氨基，取代或未取代的烷基氨基，硝基，氰基或单环杂环; R5为卤素原子或氢原子。

公开(公告)号：US20090264468A1

公开(公告)日：2009-10-22

申请号：US12456652

申请日：2009-06-19

申请人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

发明人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

IPC分类号： A61K31/454 ,  A61K31/416 ,  A61K31/4439 ,  A61K31/421 ,  A61K31/42 ,  A61P9/00 ,  A61P11/00 ,  A61P35/00 ,  A61P29/00 ,  A61P15/00

CPC分类号： C07D231/56 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04

摘要： A method for treating a disease in which Rho kinase is involved. The method is carried out by administering to a patient in need thereof a pharmaceutically effective amount of a compound of the following formula or a pharmaceutically acceptable salt thereof: , wherein the ring X is a benzene ring or a pyridine ring; R1 and R2 are hydrogen or alkyl or together form a cycloalkene ring; R3 is hydrogen, substituted alkyl, unsubstituted alkenyl, carboxyl or an ester or an amide thereof, amino or a cyano; R4 is hydrogen, hydroxyl, substituted or unsubstituted alkoxy, unsubstituted alkenyloxy, unsubstituted cycloalkyloxy, substituted or unsubstituted alkyl, unsubstituted alkenyl, unsubstituted cycloalkyl, amino, substituted or unsubstituted alkylamino, nitro, cyano or a monocyclic heterocycle; and R5 is a halogen atom or a hydrogen atom.

摘要翻译： 一种治疗涉及Rho激酶的疾病的方法。 该方法通过向有需要的患者施用药学有效量的下式化合物或其药学上可接受的盐进行：其中环X是苯环或吡啶环; R1和R2是氢或烷基或一起形成环烯烃环; R 3是氢，取代的烷基，未取代的烯基，羧基或其酯或酰胺，氨基或氰基; R4是氢，羟基，取代或未取代的烷氧基，未取代的烯氧基，未取代的环烷基氧基，取代或未取代的烷基，未取代的烯基，未被取代的环烷基，氨基，取代或未取代的烷基氨基，硝基，氰基或单环杂环; R5为卤素原子或氢原子。

公开(公告)号：US07563906B2

公开(公告)日：2009-07-21

申请号：US10575645

申请日：2004-10-15

申请人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

发明人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Takeshi Matsugi ,  Tadashi Nakajima ,  Masakazu Hatano ,  Kazutaka Kido ,  Hideaki Hara

IPC分类号： C07D233/00

CPC分类号： C07D231/56 ,  C07D401/04 ,  C07D403/04 ,  C07D413/04

摘要： An object of the present invention is to create a novel indazole derivative useful as a drug and to find a novel pharmacological action of the derivative. The compound of the present invention is represented by the formula [I] and has an excellent Rho kinase inhibiting action. In the formula, a ring X is a benzene ring or a pyridine ring; R1 and R2 are H or alkyl; R3 and R4 are halogen, H, OH, alkoxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cycloalkenyloxy, aryloxy, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, carboxy, hydrocarbonyl, alkylcarbonyl, etc.; and R5 is halogen atom, H, OH, alkoxy, aryloxy, alkyl or aryl. Each group can be substituted.

摘要翻译： 本发明的目的是产生一种可用作药物的新型吲唑衍生物，并找到该衍生物的新药理作用。 本发明的化合物由式[I]表示，具有优异的Rho激酶抑制作用。 在该式中，环X为苯环或吡啶环; R1和R2是H或烷基; R 3和R 4是卤素，H，OH，烷氧基，烯氧基，炔氧基，环烷氧基，环烯氧基，芳氧基，烷基，烯基，炔基，环烷基，环烯基，芳基，羧基，烃基，烷基羰基等。 和R 5是卤素原子，H，OH，烷氧基，芳氧基，烷基或芳基。 每组可以替代。