公开(公告)号：US08765771B2

公开(公告)日：2014-07-01

申请号：US13806940

申请日：2011-06-24

申请人： Toshiharu Morimoto ,  Tomoaki Koshizawa ,  Gen Watanabe ,  Tadaaki Ohgiya ,  Nao Yamasaki ,  Noriyuki Inoue

发明人： Toshiharu Morimoto ,  Tomoaki Koshizawa ,  Gen Watanabe ,  Tadaaki Ohgiya ,  Nao Yamasaki ,  Noriyuki Inoue

IPC分类号： A61K31/519 ,  C07D491/00

CPC分类号： C07D491/048 ,  C07D487/04 ,  C07D495/04

摘要： The present invention relates to provision of a novel compound that has an activity of promoting insulin secretion from pancreatic β cells and thus is useful as a prophylaxis and/or therapeutic agent for diseases caused by hyperglycemia such as diabetes mellitus, andthe compound represented by the following formula (1): wherein one of A and B represents a nitrogen atom and the other represents a nitrogen atom or CR10, X represents an oxygen atom, a sulfur atom or —(CH2)n-N(R12)—, Y represents an oxygen atom, a sulfur atom or —N(R13)—, and R1 to R9 each represent a hydrogen atom or another substituent, or a salt thereof, or a solvate of the compound or the salt.

摘要翻译： 本发明涉及提供一种具有促进胰腺胰岛素分泌活性的新型化合物， 细胞，因此可用作由高血糖引起的疾病如糖尿病的预防和/或治疗剂，以及由下式（1）表示的化合物：其中A和B之一表示氮原子，另一个表示 氮原子或CR 10，X表示氧原子，硫原子或 - （CH 2）n N（R 12） - ，Y表示氧原子，硫原子或-N（R 13） - ，R 1〜 原子或其它取代基，或其盐，或化合物或其盐的溶剂化物。

公开(公告)号：US20140011823A1

公开(公告)日：2014-01-09

申请号：US14005046

申请日：2012-03-13

申请人： Toru Miura ,  Seiichi Sato ,  Hajime Yamada ,  Junya Tagashira ,  Toshiaki Watanabe ,  Ryohei Sekimoto ,  Rie Ishida ,  Hitomi Aoki ,  Tadaaki Ohgiya

发明人： Toru Miura ,  Seiichi Sato ,  Hajime Yamada ,  Junya Tagashira ,  Toshiaki Watanabe ,  Ryohei Sekimoto ,  Rie Ishida ,  Hitomi Aoki ,  Tadaaki Ohgiya

IPC分类号： C07D413/14 ,  C07D401/14

CPC分类号： C07D413/14 ,  A61K31/506 ,  C07D401/14

摘要： The present invention provides: a compound represented by general formula (I) below, that has both angiotensin II receptor antagonism and a PPARγ activation effect and that is useful as a preventative and/or therapeutic agent for high blood pressure, cardiac disease, arteriosclerosis, type-2 diabetes, and the like; and a drug composition containing the compound. General formula (I) (in the formula: ring A represents a pyridine ring; ring B represents a tetrazole ring or an oxadiazol-5(4H)-one ring; X represents C—R5 or a nitrogen atom; R1 represents an alkyl group; R2 represents an alkyl group or a cycloalkyl group; and R3, R4, and R5 each independently represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group or similar.

摘要翻译： 本发明提供：下述通式（I）表示的化合物，既具有血管紧张素II受体拮抗作用又具有PPARγ活化作用，可用作高血压，心脏病，动脉硬化等的预防和/或治疗剂， 2型糖尿病等; 和含有该化合物的药物组合物。 通式（I）（式中，环A表示吡啶环;环B表示四唑环或恶二唑-5（4H） - 酮环; X表示C-R5或氮原子; R1表示烷基 ; R 2表示烷基或环烷基; R 3，R 4和R 5各自独立地表示氢原子，卤素原子，烷基，烷氧基等。

公开(公告)号：US20130225618A1

公开(公告)日：2013-08-29

申请号：US13824782

申请日：2011-10-03

申请人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takeshi Murakami

发明人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takeshi Murakami

IPC分类号： A61K31/505

CPC分类号： A61K31/505 ,  C07D239/47

摘要： The present invention is intended to provide a pharmaceutical product for inhibiting expression of at least one lipid metabolism related mRNA selected from the group consisting of Angptl4 mRNA, SCD-1 mRNA, and SREBP1c mRNA, the present invention is also intended to provide a preventive and/or therapeutic agent for various diseases based on inhibition of expression of at least one lipid metabolism related mRNA selected from the group consisting of Angptl4 mRNA, SCD-1 mRNA, and SREBP1c mRNA, and the present invention relates to an agent for inhibiting expression of at least one lipid metabolism related mRNA selected from the group consisting of Angptl4 mRNA, SCD-1 mRNA, and SREBP1c mRNA, and relates also to a preventive and/or therapeutic agent for various diseases based on the inhibition of the expression of at least one lipid metabolism related mRNA selected from the group consisting of Angptl4 mRNA, SCD-1 mRNA, and SREBP1c mRNA, the agent comprising a compound represented by Formula (I), its salt, or a solvate of any of them as an active ingredient: wherein the symbols are the same as those given in the description.

公开(公告)号：US20120322819A1

公开(公告)日：2012-12-20

申请号：US13580056

申请日：2011-02-25

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

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

IPC分类号： A61K31/506 ,  C07D413/14 ,  A61P9/00 ,  A61P3/04 ,  A61P9/10 ,  A61P3/00 ,  A61P3/10 ,  C07D413/10 ,  A61P9/12

CPC分类号： C07D413/10 ,  C07D413/14

摘要： Disclosed is novel compound and medicinal formulation containing same, possessing both angiotensin II receptor blocking and PPARγ activation effect, of use as a medicine for prevention and/or treatment of hypertension, heart disease, angina pectoris, cerebrovascular disorder, cerebral circulatory disturbances, post-ischemic peripheral circulatory damage, renal disease, arteriosclerosis, inflammatory disorder, type 2 diabetes, diabetic complications, insulin resistance syndrome, syndrome X, metabolic syndrome and hyperinsulinaemia. Further disclosed is the general formula I (where one or both of R1 and R2 represent a C1-6 alkyl group, R3 represents a C1-6 alkyl group which may contain one or more substituent groups selected from group A, or a C3-8 cycloalkyl group which may contain one or more substituent groups selected from group B.) which represents the compound, and salts thereof, solvates thereof, and medicinal compositions containing any of these.

摘要翻译： 公开了含有血管紧张素II受体阻断和PPARγ活化作用的新型化合物和药物制剂，用作预防和/或治疗高血压，心脏病，心绞痛，脑血管障碍，脑循环障碍， 缺血性外周循环损伤，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。 进一步公开的是通式I（其中R 1和R 2中的一个或两个表示C 1-6烷基，R 3表示可以含有一个或多个选自A组的取代基的C 1-6烷基或C 3-8 可以含有一个或多个选自B组的取代基的环烷基），其代表该化合物及其盐，其溶剂合物，以及含有这些中的任何一种的药物组合物。

公开(公告)号：US20120165353A1

公开(公告)日：2012-06-28

申请号：US13394266

申请日：2010-09-29

申请人： Toru Miura ,  Seiichi Sato ,  Hajime Yamada ,  Junya Tagashira ,  Ryohei Sekimoto ,  Rie Ishida ,  Hitomi Aoki ,  Tadaaki Ohgiya

发明人： Toru Miura ,  Seiichi Sato ,  Hajime Yamada ,  Junya Tagashira ,  Ryohei Sekimoto ,  Rie Ishida ,  Hitomi Aoki ,  Tadaaki Ohgiya

IPC分类号： A61K31/506 ,  C07D413/14 ,  A61P9/00 ,  A61P13/12 ,  A61P3/10 ,  A61P9/10 ,  A61P9/12 ,  C07D401/14 ,  A61P3/00

CPC分类号： C07D401/14 ,  A61K31/422 ,  A61K31/4427 ,  C07D413/14

摘要： Disclosed are: a novel compound which has both an antagonistic activity on an angiotensin II receptor and a PPARγ-activating activity and is therefore useful as a prophylactic and/or therapeutic agent for hypertension, heart diseases, arteriosclerosis, type-2 diabetes, diabetic complications, metabolic syndrome or the like; and a pharmaceutical composition containing the compound. Specifically disclosed are: a compound represented by general formula (I) (wherein the ring A represents a pyridine ring; the ring B represents a tetrazole ring or an oxadiazol-5(4H)-one ring; X represents C—R5 or a nitrogen atom; R1 represents a C1-6 alkyl group; R2 represents a C1-6 alkyl group or a C3-8 cycloalkyl group; and R3, R4, R5 independently represent a hydrogen atom, a halogen atom, a C1-6 alkyl group, a halo-C1-6 alkyl group, or a C1-6 alkoxy group which may have a substituent), a salt of the compound, or a solvate of the compound or the salt; and a pharmaceutical composition containing the compound, the salt or the solvate.

摘要翻译： 公开了一种对血管紧张素II受体具有拮抗作用和PPARγ活化活性的新型化合物，因此可用作高血压，心脏病，动脉硬化，2型糖尿病，糖尿病并发症的预防和/或治疗剂 ，代谢综合征等; 和含有该化合物的药物组合物。 具体公开的是：由通式（I）表示的化合物（其中环A表示吡啶环;环B表示四唑环或恶二唑-5（4H） - 酮环; X表示C-R5或氮 原子; R1表示C1-6烷基; R2表示C1-6烷基或C3-8环烷基; R3，R4，R5分别表示氢原子，卤素原子，C1-6烷基， 卤代C 1-6烷基或可具有取代基的C 1-6烷氧基），化合物的盐或化合物或其盐的溶剂合物; 和含有该化合物，该盐或溶剂化物的药物组合物。

公开(公告)号：US08012989B2

公开(公告)日：2011-09-06

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： A61K31/505

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。

公开(公告)号：US07750150B2

公开(公告)日：2010-07-06

申请号：US10545200

申请日：2004-02-27

申请人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takayuki Matsuda

发明人： Kimiyuki Shibuya ,  Tadaaki Ohgiya ,  Takayuki Matsuda

IPC分类号： C07D243/00 ,  C07D241/04 ,  C07D295/00

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：US20080119474A1

公开(公告)日：2008-05-22

申请号：US12013691

申请日：2008-01-14

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 ,  A61P19/00 ,  A61P9/00 ,  A61P37/00

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 (substituted) 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）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产生具有优异的抑制活性，并且可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防和治疗。

公开(公告)号：US06664256B1

公开(公告)日：2003-12-16

申请号：US09612953

申请日：2000-07-10

申请人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Natsuyo Kumai ,  Kyoko Kotaki

发明人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Natsuyo Kumai ,  Kyoko Kotaki

IPC分类号： A61K3150

CPC分类号： C07D401/12 ,  A61K31/50 ,  C07D237/08 ,  C07D237/12 ,  C07D237/14 ,  C07D237/18 ,  C07D237/20 ,  C07D237/24 ,  C07D405/04 ,  C07D417/04

摘要： Phenylpyridazine compounds represented by the following formula (I): are provided, wherein R1, R2, R3, R4, and n are as defined herein having excellent inhibitory activity against interleukin-1&bgr; production, and useful in the treatment of prevention of diseases caused by stimulation of interleukin-1&bgr; production, such as immune system diseases, inflammatory diseases, and ischemic diseases.

摘要翻译： 提供由下式（I）表示的苯基哒嗪化合物：其中R 1，R 2，R 3，R 4和n如本文所定义，对白细胞介素-1β生产具有优异的抑制活性 可用于治疗由免疫系统疾病，炎症性疾病和缺血性疾病等白细胞介素-1β产生刺激引起的疾病的预防。

公开(公告)号：US09315493B2

公开(公告)日：2016-04-19

申请号：US14005046

申请日：2012-03-13

申请人： Toru Miura ,  Seiichi Sato ,  Hajime Yamada ,  Junya Tagashira ,  Toshiaki Watanabe ,  Ryohei Sekimoto ,  Rie Ishida ,  Hitomi Aoki ,  Tadaaki Ohgiya

发明人： Toru Miura ,  Seiichi Sato ,  Hajime Yamada ,  Junya Tagashira ,  Toshiaki Watanabe ,  Ryohei Sekimoto ,  Rie Ishida ,  Hitomi Aoki ,  Tadaaki Ohgiya

IPC分类号： A61K31/505 ,  C07D413/14 ,  C07D401/14 ,  A61K31/506

CPC分类号： C07D413/14 ,  A61K31/506 ,  C07D401/14

摘要： The present invention provides: a compound represented by general formula (I) below, that has both angiotensin II receptor antagonism and a PPARγ activation effect and that is useful as a preventative and/or therapeutic agent for high blood pressure, cardiac disease, arteriosclerosis, type-2 diabetes, and the like; and a drug composition containing the compound. General formula (I) (in the formula: ring A represents a pyridine ring; ring B represents a tetrazole ring or an oxadiazol-5(4H)-one ring; X represents C—R5 or a nitrogen atom; R1 represents an alkyl group; R2 represents an alkyl group or a cycloalkyl group; and R3, R4, and R5 each independently represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group or similar.

摘要翻译： 本发明提供：下述通式（I）表示的化合物，其具有血管紧张素II受体拮抗作用和PPARγ活化作用，可用作高血压，心脏病，动脉硬化等的预防和/或治疗剂， 2型糖尿病等; 和含有该化合物的药物组合物。 通式（I）（式中，环A表示吡啶环;环B表示四唑环或恶二唑-5（4H） - 酮环; X表示C-R5或氮原子; R1表示烷基 ; R 2表示烷基或环烷基; R 3，R 4和R 5各自独立地表示氢原子，卤素原子，烷基，烷氧基等。