公开(公告)号：US20070049595A1

公开(公告)日：2007-03-01

申请号：US11590811

申请日：2006-11-01

申请人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Yukiyoshi Yamazaki ,  Natsuyo Kumai ,  Kyoko Kotaki ,  Hideo Yoshizaki ,  Yuriko Habata

发明人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Yukiyoshi Yamazaki ,  Natsuyo Kumai ,  Kyoko Kotaki ,  Hideo Yoshizaki ,  Yuriko Habata

IPC分类号： A61K31/50 ,  C07D237/02

CPC分类号： C07D401/04 ,  C07D237/02 ,  C07D237/04 ,  C07D237/14 ,  C07D237/18 ,  C07D401/06 ,  C07D401/14 ,  C07D413/04

摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1β production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.

摘要翻译： 本发明涉及由式（1）表示的哒嗪衍生物：其中R 1表示（取代的）芳基，R 2表示在4位被取代的苯基 通过低级烷氧基或低级烷硫基，R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代的）芳基，（取代的）芳氧基 ，（取代）的含氮杂环残基，（取代）氨基羰基或低级烷基羰基，A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线 表示4-位和5-位之间的碳 - 碳键是单键或双键，或其盐; 以及含有它们作为有效成分的药物。 这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

公开(公告)号：US20060160804A1

公开(公告)日：2006-07-20

申请号：US11385995

申请日：2006-03-22

申请人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Yukiyoshi Yamazaki ,  Natsuyo Kumai ,  Kyoko Kotaki ,  Hideo Yoshizaki ,  Yuriko Habata

发明人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Yukiyoshi Yamazaki ,  Natsuyo Kumai ,  Kyoko Kotaki ,  Hideo Yoshizaki ,  Yuriko Habata

IPC分类号： A61K31/5377 ,  A61K31/501 ,  C07D413/02 ,  C07D403/02

CPC分类号： C07D401/04 ,  C07D237/02 ,  C07D237/04 ,  C07D237/14 ,  C07D237/18 ,  C07D401/06 ,  C07D401/14 ,  C07D413/04

摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1β production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.

摘要翻译： 本发明涉及由式（1）表示的哒嗪衍生物：其中R 1表示（取代的）芳基，R 2表示在4位被取代的苯基 通过低级烷氧基或低级烷硫基，R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代的）芳基，（取代的）芳氧基 ，（取代）的含氮杂环残基，（取代）氨基羰基或低级烷基羰基，A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线 表示4-位和5-位之间的碳 - 碳键是单键或双键，或其盐; 以及含有它们作为有效成分的药物。 这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

公开(公告)号：US20050131002A1

公开(公告)日：2005-06-16

申请号：US10985938

申请日：2004-11-09

申请人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Hirata

发明人： Kimiyuki Shibuya ,  Toru Miura ,  Katsumi Kawamine ,  Yukihiro Sato ,  Tadaaki Ohgiya ,  Takahiro Kitamura ,  Chiyoka Ozaki ,  Toshiyuki Edano ,  Mitsuteru Hirata

IPC分类号： A61K31/4439 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D498/04 ,  C07D513/04 ,  A61K31/506 ,  C07D413/02 ,  C07D417/02 ,  C07D43/02

CPC分类号： C07D403/12 ,  A61K31/4439 ,  C07D401/12 ,  C07D413/12 ,  C07D417/12 ,  C07D513/04

摘要： The present invention provides to a novel compound having an ACAT inhibiting activity. The present invention relates to compounds represented by formula (I) wherein represents an optionally substituted divalent residue such as benzene, pyridine, cyclohexane or naphthalene, or a group, Het represents a 5- to 8-membered, substituted or unsubstituted heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, such as a monocyclic group, a polycyclic group or a group of a fused ring, X represents —NH—, an oxygen atom or a sulfur atom, Y represents —NR4—, an oxygen atom, a sulfur atom, a sulfoxide or a sulfone, Z represents a single bond or —NR5—, R4 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, R5 represents a hydrogen atom, a lower alkyl group, an aryl group or an optionally substituted silyl lower alkyl group, and n is an integer of from 1 to 15, or salts or solvates thereof, and a pharmaceutical composition containing at least one of these compounds.

摘要翻译： 本发明提供具有ACAT抑制活性的新型化合物。 本发明涉及由式（I）表示的化合物，其中表示任选取代的二价残基例如苯，吡啶，环己烷或萘，或者基团，Het表示5至8元，取代或未取代的杂环基， 至少一个选自氮原子，氧原子和硫原子的杂原子，如单环基团，多环基团或稠环基团，X表示-NH-，氧原子或硫原子 原子，Y表示-NR 4 - ，氧原子，硫原子，亚砜或砜，Z表示单键或-NR 5 - ， - R 4表示氢原子，低级烷基，芳基或任选取代的甲硅烷基低级烷基，R 5表示氢原子，低级烷基，芳基 基团或任选取代的甲硅烷基低级烷基，n为1至15的整数，或其盐或溶剂化物， d含有这些化合物中的至少一种的药物组合物。

公开(公告)号：US06348468B1

公开(公告)日：2002-02-19

申请号：US09530949

申请日：2000-05-15

申请人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Yukiyoshi Yamazaki ,  Natsuyo Kumai ,  Kyoko Kotaki ,  Hideo Yoshizaki ,  Yuriko Habata

发明人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Yukiyoshi Yamazaki ,  Natsuyo Kumai ,  Kyoko Kotaki ,  Hideo Yoshizaki ,  Yuriko Habata

IPC分类号： A61K31501

CPC分类号： C07D401/04 ,  C07D237/02 ,  C07D237/04 ,  C07D237/14 ,  C07D237/18 ,  C07D401/06 ,  C07D401/14 ,  C07D413/04

摘要： This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1&bgr; production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.

摘要翻译： 本发明涉及由式（1）表示的哒嗪衍生物：其中R1表示（取代的）芳基，R2表示通过低级烷氧基或低级烷硫基在4位被取代的苯基，R3表示低级烷氧基 基团，卤代低级烷基，低级环烷基，（取代的）芳基，（取代的）芳氧基，（取代的）含氮杂环残基，（取代的）氨基羰基或低级烷基羰基， A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线表示4-位和5-位之间的碳 - 碳键为单键或双键 键或其盐; 以及含有它们作为有效成分的药物。 这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

公开(公告)号：US09045460B2

公开(公告)日：2015-06-02

申请号：US13816534

申请日：2011-08-25

申请人： Noriaki Gomi ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

发明人： Noriaki Gomi ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

IPC分类号： C07D401/12 ,  C07D243/08

CPC分类号： C07D401/12 ,  C07D243/08

摘要： The present invention provides a method capable of industrially producing a target product, i.e., a compound represented by the aforementioned formula (I) or a salt thereof, which is useful for preventing and treating cerebrovascular disorders such as cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, and cerebral edema, particularly for preventing and treating glaucoma, at high yield even on a large scale without imposing a negative impact on the environment. The present invention provides a method for producing a compound represented by formula (I) or a salt thereof, wherein the method comprises a step of reacting a compound represented by formula (III) or a salt thereof with a compound represented by formula (II) in the presence of at least one solvent selected from the group consisting of a nitrile solvent, an amide solvent, a sulfoxide solvent, and a urea solvent, and a base.

摘要翻译： 本发明提供一种能够工业生产目标产物的方法，即由上述式（I）表示的化合物或其盐，其可用于预防和治疗脑梗塞，脑出血，蛛网膜下腔出血等脑血管疾病 ，脑水肿，特别是预防和治疗青光眼，即使大规模高产，也不会对环境造成负面影响。 本发明提供一种由式（I）表示的化合物或其盐的制备方法，其中所述方法包括使式（III）表示的化合物或其盐与式（II）表示的化合物反应的步骤， 在选自腈溶剂，酰胺溶剂，亚砜溶剂和尿素溶剂中的至少一种溶剂和碱存在下进行。

公开(公告)号：US20130144054A1

公开(公告)日：2013-06-06

申请号：US13816534

申请日：2011-08-25

申请人： Noriaki Gomi ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

发明人： Noriaki Gomi ,  Tadaaki Ohgiya ,  Kimiyuki Shibuya

IPC分类号： C07D401/12 ,  C07D243/08

CPC分类号： C07D401/12 ,  C07D243/08

摘要： The present invention provides a method capable of industrially producing a target product, i.e., a compound represented by the aforementioned formula (I) or a salt thereof, which is useful for preventing and treating cerebrovascular disorders such as cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, and cerebral edema, particularly for preventing and treating glaucoma, at high yield even on a large scale without imposing a negative impact on the environment. The present invention provides a method for producing a compound represented by formula (I) or a salt thereof, wherein the method comprises a step of reacting a compound represented by formula (III) or a salt thereof with a compound represented by formula (II) in the presence of at least one solvent selected from the group consisting of a nitrile solvent, an amide solvent, a sulfoxide solvent, and a urea solvent, and a base.

公开(公告)号：US20120028983A1

公开(公告)日：2012-02-02

申请号：US13263023

申请日：2010-04-16

申请人： Toru Miura ,  Kazuhiro Onogi ,  Seiichi Sato ,  Junya Tagashira ,  Gen Watanabe ,  Ryohei Sekimoto ,  Rie Ishida ,  Hitomi Aoki ,  Tadaaki Ohgiya

发明人： Toru Miura ,  Kazuhiro Onogi ,  Seiichi Sato ,  Junya Tagashira ,  Gen Watanabe ,  Ryohei Sekimoto ,  Rie Ishida ,  Hitomi Aoki ,  Tadaaki Ohgiya

IPC分类号： A61K31/53 ,  C07D403/14 ,  C07D413/14 ,  C07D417/14 ,  A61P13/12 ,  A61P3/00 ,  A61P3/10 ,  A61P9/00 ,  A61P9/10 ,  A61P9/12 ,  C07D401/14 ,  A61K31/513

CPC分类号： C07D401/14 ,  C07D403/14 ,  C07D413/14 ,  C07D417/14

摘要： Disclosed is a compound which has both an angiotensin-II receptor antagonistic activity and a PPARγ activation activity and is useful as a prophylactic and/or therapeutic agent for hypertension, heart diseases, angina pectoris, cerebrovascular disorders, cerebral circulatory disorders, ischemic peripheral circulatory disorders, renal diseases, arteriosclerosis, inflammatory diseases, type-2 diabetes, diabetic complications, insulin resistance syndrome, syndrome X, metabolic syndrome and hyperinsulinemia. [In the formula, A represents a 5- to 10-membered heteroaryl group; R1 and R2 independently represent a C1-6 alkyl group; and each of R3 to R5 is absent or represents H, a halogen atom, OH, NO2, a halo-C1-6 alkyl group, a (substituted) C1-6 alkoxy group, a (substituted) C3-6 cycloalkyloxy group, or a 5- to 10-membered heteroaryl group.]

摘要翻译： 公开了具有血管紧张素-II受体拮抗作用和PPARγ活化活性的化合物，可用作高血压，心脏病，心绞痛，脑血管病，脑循环障碍，缺血性外周循环障碍的预防和/或治疗剂 肾脏疾病，动脉硬化，炎性疾病，2型糖尿病，糖尿病并发症，胰岛素抵抗综合征，X综合征，代谢综合征和高胰岛素血症。 [式中，A表示5至10元杂芳基; R1和R2独立地表示C1-6烷基; 并且R 3至R 5不存在或表示H，卤素原子，OH，NO 2，卤代C 1-6烷基，（取代的）C 1-6烷氧基，（取代的）C 3-6环烷氧基或 5至10元杂芳基。]

公开(公告)号：US20100249148A1

公开(公告)日：2010-09-30

申请号：US12815905

申请日：2010-06-15

申请人： Tadaaki OHGIYA ,  Toru MIURA ,  Ayumu OKUDA ,  Toshiharu ARAI ,  Koichi YAMAZAKI ,  Taro AOKI ,  Katsutoshi MIYOSAWA ,  Haruki SHIBATA ,  Kimiyuki SHIBUYA

发明人： Tadaaki OHGIYA ,  Toru MIURA ,  Ayumu OKUDA ,  Toshiharu ARAI ,  Koichi YAMAZAKI ,  Taro AOKI ,  Katsutoshi MIYOSAWA ,  Haruki SHIBATA ,  Kimiyuki SHIBUYA

IPC分类号： A61K31/506 ,  C07D401/12 ,  C07D471/04 ,  C07D403/12 ,  A61P9/10 ,  A61P3/06

CPC分类号： C07D401/12 ,  C07D403/12 ,  C07D471/04

摘要： A compound represented by the following general formula (I), wherein R1, R2, R3, R4 and R5 represent hydrogen atom, a halogen atom, a lower alkyl group and the like, R6 represents an alkyl group, a cycloalkyl group and the like, R7 and R8 represent hydrogen atom, a lower alkyl group, a (lower cycloalkyl)(lower alkyl) group and the like, R9 represents hydrogen atom, a halogen atom, a lower alkoxy group and the like, R10 and R11 represent hydrogen atom, a lower alkyl group, a lower alkoxy group, a halo(lower alkyl) group and the like, and A represents a heterocyclic ring constituted by 6 to 10 atoms, which has potent inhibitory activity on cholesterol ester transfer protein (CETP).

摘要翻译： 由下列通式（I）表示的化合物，其中R 1，R 2，R 3，R 4和R 5表示氢原子，卤原子，低级烷基等，R 6表示烷基，环烷基等 ，R7和R8表示氢原子，低级烷基，（低级环烷基）（低级烷基）等，R9表示氢原子，卤素原子，低级烷氧基等，R10和R11表示氢原子 ，低级烷基，低级烷氧基，卤代（低级烷基）等，A表示6〜10个原子构成的杂环，对胆固醇酯转移蛋白（CETP）具有有效的抑制活性。

公开(公告)号：US20100234599A1

公开(公告)日：2010-09-16

申请号：US12762111

申请日：2010-04-16

申请人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takayuki Matsuda

发明人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takayuki Matsuda

IPC分类号： C07D413/14 ,  C07D417/14

CPC分类号： A61K31/496 ,  C07D401/12

摘要： This invention relates to a method for preparing an acid addition salt of a polyacidic basic compound, or a water adduct having basic site(s) stronger than pyridine. The method comprises reacting the polyacidic basic compound with an acid salt of pyridine.By the present invention, the number of moles of an added acid in the acid addition salt of the polyacidic basic compound can be readily changed to a number suited for the polyacidic basic compound as needed.

摘要翻译： 本发明涉及一种制备多酸碱性化合物的酸加成盐的方法或具有比吡啶强的碱性位点的水加合物。 该方法包括使多酸碱性化合物与吡啶的酸式盐反应。 通过本发明，可以根据需要容易地将多酸碱性化合物的酸加成盐中加入的酸的摩尔数变更为适合于多酸碱性化合物的数量。

公开(公告)号：US07790737B2

公开(公告)日：2010-09-07

申请号：US12045982

申请日：2008-03-11

申请人： Tadaaki Ohgiya ,  Toru Miura ,  Ayumu Okuda ,  Toshiharu Arai ,  Koichi Yamazaki ,  Taro Aoki ,  Katsutoshi Miyosawa ,  Haruki Shibata ,  Kimiyuki Shibuya

发明人： Tadaaki Ohgiya ,  Toru Miura ,  Ayumu Okuda ,  Toshiharu Arai ,  Koichi Yamazaki ,  Taro Aoki ,  Katsutoshi Miyosawa ,  Haruki Shibata ,  Kimiyuki Shibuya

IPC分类号： A61K31/505

CPC分类号： C07D401/12 ,  C07D403/12 ,  C07D471/04

摘要： A compound represented by the following general formula (I), wherein R1, R2, R3, R4 and R5 represent hydrogen atom, a halogen atom, a lower alkyl group and the like, R6 represents an alkyl group, a cycloalkyl group and the like, R7 and R8 represent hydrogen atom, a lower alkyl group, a (lower cycloalkyl)(lower alkyl) group and the like, R9 represents hydrogen atom, a halogen atom, a lower alkoxy group and the like, R10 and R11 represent hydrogen atom, a lower alkyl group, a lower alkoxy group, a halo(lower alkyl) group and the like, and A represents a heterocyclic ring constituted by 6 to 10 atoms, which has potent inhibitory activity on cholesterol ester transfer protein (CETP).

摘要翻译： 由下列通式（I）表示的化合物，其中R 1，R 2，R 3，R 4和R 5表示氢原子，卤原子，低级烷基等，R 6表示烷基，环烷基等 ，R7和R8表示氢原子，低级烷基，（低级环烷基）（低级烷基）等，R9表示氢原子，卤素原子，低级烷氧基等，R10和R11表示氢原子 ，低级烷基，低级烷氧基，卤代（低级烷基）等，A表示6〜10个原子构成的杂环，对胆固醇酯转移蛋白（CETP）具有有效的抑制活性。