公开(公告)号：US08816092B2

公开(公告)日：2014-08-26

申请号：US13699410

申请日：2011-05-26

申请人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Yasunori Tsuzaki ,  Akira Takama ,  Kazutaka Kido ,  Tomokazu Fujimoto ,  Takeshi Matsugi

发明人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Yasunori Tsuzaki ,  Akira Takama ,  Kazutaka Kido ,  Tomokazu Fujimoto ,  Takeshi Matsugi

IPC分类号： A61K31/44 ,  C07D401/00 ,  C07D401/14 ,  C07D401/10 ,  C07D405/14 ,  C07D401/04

CPC分类号： C07D401/14 ,  C07D401/04 ,  C07D401/10 ,  C07D405/14

摘要： A compound represented by formula (1) or salt thereof and a production intermediate thereof are created. The compound exhibited an excellent antioxidation action in a microsome lipid peroxidation measuring system using a rat liver microsome. Therefore, the compound or salt thereof is useful as an antioxidant. The present invention also provides use of a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof for production of an antioxidant.

摘要翻译： 产生由式（1）表示的化合物或其盐及其制备中间体。 该化合物在使用大鼠肝微粒体的微粒体脂质过氧化测定系统中表现出优异的抗氧化作用。 因此，其化合物或其盐可用作抗氧化剂。 本发明还提供由式（1）表示的化合物或其药学上可接受的盐在抗氧化剂的制备中的用途。

公开(公告)号：US20130102787A1

公开(公告)日：2013-04-25

申请号：US13699410

申请日：2011-05-26

申请人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Yasunori Tsuzaki ,  Akira Takama ,  Kazutaka Kido ,  Tomokazu Fujimoto ,  Takeshi Matsugi

发明人： Masahiko Hagihara ,  Ken-ichi Komori ,  Hidetoshi Sunamoto ,  Hiroshi Nishida ,  Yasunori Tsuzaki ,  Akira Takama ,  Kazutaka Kido ,  Tomokazu Fujimoto ,  Takeshi Matsugi

IPC分类号： C07D401/14 ,  C07D401/10

CPC分类号： C07D401/14 ,  C07D401/04 ,  C07D401/10 ,  C07D405/14

摘要： A compound represented by formula (1) or salt thereof and a production intermediate thereof are created. The compound exhibited an excellent antioxidation action in a microsome lipid peroxidation measuring system using a rat liver microsome. Therefore, the compound or salt thereof is useful as an antioxidant. The present invention also provides use of a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof for production of an antioxidant.

摘要翻译： 产生由式（1）表示的化合物或其盐及其制备中间体。 该化合物在使用大鼠肝微粒体的微粒体脂质过氧化测定系统中表现出优异的抗氧化作用。 因此，其化合物或其盐可用作抗氧化剂。 本发明还提供由式（1）表示的化合物或其药学上可接受的盐在抗氧化剂的制备中的用途。

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：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：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。

公开(公告)号：US20130109653A1

公开(公告)日：2013-05-02

申请号：US13809115

申请日：2011-07-08

申请人： Tsuyoshi Nakamura ,  Hidenori Namiki ,  Naoki Terasaka ,  Akiko Shima ,  Masahiko Hagihara ,  Noriaki Iwase ,  Katsunori Takata ,  Osamu Kikuchi ,  Kazunari Tsuboike ,  Hiroyuki Setoguchi ,  Kenji Yoneda ,  Hidetoshi Sunamoto ,  Koji Ito

发明人： Tsuyoshi Nakamura ,  Hidenori Namiki ,  Naoki Terasaka ,  Akiko Shima ,  Masahiko Hagihara ,  Noriaki Iwase ,  Katsunori Takata ,  Osamu Kikuchi ,  Kazunari Tsuboike ,  Hiroyuki Setoguchi ,  Kenji Yoneda ,  Hidetoshi Sunamoto ,  Koji Ito

IPC分类号： C07D401/14 ,  C07D417/14 ,  C07F7/18 ,  C07D413/14

CPC分类号： C07D401/14 ,  C07D413/14 ,  C07D417/14 ,  C07F7/1804

摘要： The present invention provides a substituted pyridine compound or a pharmacologically acceptable salt thereof which has excellent CETP inhibition activity and is useful as a medicament. The present invention provides a compound represented by a general formula (I), wherein R1 is H, optionally substituted alkyl, OH, optionally substituted alkoxy, alkylsulfonyl, optionally substituted amino, carboxy, optionally substituted carbonyl, CN, halogeno, optionally substituted phenyl, optionally substituted aromatic heterocyclyl, optionally substituted saturated heterocyclyl, optionally substituted saturated heterocyclyloxy or optionally substituted saturated heterocyclylcarbonyl, etc., and the like.

摘要翻译： 本发明提供了具有优异的CETP抑制活性并可用作药物的取代的吡啶化合物或其药学上可接受的盐。 本发明提供由通式（I）表示的化合物，其中R 1为H，任选取代的烷基，OH，任选取代的烷氧基，烷基磺酰基，任选取代的氨基，羧基，任选取代的羰基，CN，卤代，任选取代的苯基， 任选取代的芳族杂环基，任选取代的饱和杂环基，任选取代的饱和杂环氧基或任选取代的饱和杂环基羰基等，等等。

公开(公告)号：US20140213549A9

公开(公告)日：2014-07-31

申请号：US13809115

申请日：2011-07-08

申请人： Tsuyoshi Nakamura ,  Hidenori Namiki ,  Naoki Terasaka ,  Akiko Shima ,  Masahiko Hagihara ,  Noriaki Iwase ,  Katsunori Takata ,  Osamu Kikuchi ,  Kazunari Tsuboike ,  Hiroyuki Setoguchi ,  Kenji Yoneda ,  Hidetoshi Sunamoto ,  Koji Ito

发明人： Tsuyoshi Nakamura ,  Hidenori Namiki ,  Naoki Terasaka ,  Akiko Shima ,  Masahiko Hagihara ,  Noriaki Iwase ,  Katsunori Takata ,  Osamu Kikuchi ,  Kazunari Tsuboike ,  Hiroyuki Setoguchi ,  Kenji Yoneda ,  Hidetoshi Sunamoto ,  Koji Ito

IPC分类号： C07D401/14 ,  C07D417/14 ,  C07F7/18 ,  C07D413/14

CPC分类号： C07D401/14 ,  C07D413/14 ,  C07D417/14 ,  C07F7/1804

摘要： The present invention provides a substituted pyridine compound or a pharmacologically acceptable salt thereof which has excellent CETP inhibition activity and is useful as a medicament. The present invention provides a compound represented by a general formula (I), wherein R1 is H, optionally substituted alkyl, OH, optionally substituted alkoxy, alkylsulfonyl, optionally substituted amino, carboxy, optionally substituted carbonyl, CN, halogeno, optionally substituted phenyl, optionally substituted aromatic heterocyclyl, optionally substituted saturated heterocyclyl, optionally substituted saturated heterocyclyloxy or optionally substituted saturated heterocyclylcarbonyl, etc., and the like.

摘要翻译： 本发明提供了具有优异的CETP抑制活性并可用作药物的取代的吡啶化合物或其药学上可接受的盐。 本发明提供由通式（I）表示的化合物，其中R 1为H，任选取代的烷基，OH，任选取代的烷氧基，烷基磺酰基，任选取代的氨基，羧基，任选取代的羰基，CN，卤代，任选取代的苯基， 任选取代的芳族杂环基，任选取代的饱和杂环基，任选取代的饱和杂环氧基或任选取代的饱和杂环基羰基等，等等。