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：US20130102621A1

公开(公告)日：2013-04-25

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： C07D491/048 ,  C07D487/04 ,  C07D495/04

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： 本发明涉及提供具有促进胰β细胞胰岛素分泌的活性的新型化合物，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）：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） - ，并且R 1至R 9各自表示氢原子或其它取代基，或其盐，或化合物或其盐的溶剂合物。

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：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：US08664226B2

公开(公告)日：2014-03-04

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： C07D401/14 ,  A61K31/506

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，脑血管障碍，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：US20120264753A1

公开(公告)日：2012-10-18

申请号：US13511876

申请日：2010-12-22

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

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

IPC分类号： A61K31/4178 ,  A61K31/4245 ,  C07D413/14 ,  A61K31/506 ,  C07D403/14 ,  A61K31/5377 ,  C07D403/10 ,  A61P9/00 ,  A61P9/12 ,  A61P9/10 ,  A61P13/12 ,  A61P3/00 ,  A61P3/10 ,  A61P25/00 ,  C07D413/10

CPC分类号： C07D403/10 ,  C07D403/14 ,  C07D413/10 ,  C07D413/14

摘要： Disclosed is a novel 1-(biphenyl-4-yl-methyl)-1H-imidazole derivative represented by general formula (I), which has both angiotensin II receptor antagonist activity and PPAR-γ activating activity and is useful as a prophylactic and/or therapeutic agent for cardiovascular diseases and metabolic diseases. Also disclosed is a pharmaceutical composition which contains the novel 1-(biphenyl-4-yl-methyl)-1H-imidazole derivative. In general formula (I), ring A represents a group represented by formula (II) or (III); R1 represents a C1-6 alkyl group; R2 represents a C1-6 alkyl group which may be substituted by a hydroxy group, or a group represented by formula —CO—R4 (wherein R4 represents a hydroxy group, a C1-6 alkoxy group, an amino group, a mono(C1-6 alkyl)amino group, a di(C1-6 alkyl)amino group, a morpholino group, a piperidino group or a pyrrolidino group); R3 represents a halogen atom or a C1-6 alkoxy group; and X and Y may be the same or different and each represents a nitrogen atom or CH.

摘要翻译： 公开了由通式（I）表示的新颖的1-（联苯-4-基 - 甲基）-1H-咪唑衍生物，其具有血管紧张素II受体拮抗剂活性和PPAR-γ活化活性，可用作预防和/ 或用于心血管疾病和代谢疾病的治疗剂。 还公开了含有新的1-（联苯-4-基 - 甲基）-1H-咪唑衍生物的药物组合物。 在通式（I）中，环A表示由式（II）或（III）表示的基团; R1表示C1-6烷基; R2表示可以被羟基取代的C1-6烷基或由式-CO-R4表示的基团（其中R4表示羟基，C1-6烷氧基，氨基，单（C1 -6烷基）氨基，二（C 1-6烷基）氨基，吗啉代基，哌啶子基或吡咯烷子基）。 R3表示卤素原子或C1-6烷氧基; X和Y可以相同或不同，各自表示氮原子或CH。

公开(公告)号：US20120046308A1

公开(公告)日：2012-02-23

申请号：US13318750

申请日：2010-05-28

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 ,  C07D401/14 ,  A61P9/00 ,  A61P9/12 ,  A61P9/10 ,  C07D239/52 ,  A61P3/10

CPC分类号： C07D401/04 ,  C07D239/34 ,  C07D239/36 ,  C07D401/06 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D413/14

摘要： An α-phenoxybenzeneacetic acid derivative represented by general formula (I), 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, metabolic syndrome or the like, a salt of the derivative, or a solvate of the derivative or the salt; and a pharmaceutical composition containing the derivative, the salt or the solvate. [In the formula, Q represents a group represented by formula (II) or (III) [wherein R1 and R1′ independently represent a C1-6 alkyl group; R2 and R2′ independently represent a substituted or unsubstituted C1-6 alkyl group; R3 represents a hydrogen atom, a substituted or unsubstituted C1-6 alkyl group, or a group represented by formula (IV) [wherein X and Y independently represent CH or N; Z represents a C1-6 alkylene chain, or the like; R11 represents a hydrogen atom, a C6-10 aryl group, or the like; and m represents 0 or 1]; and R4 represents a substituted C1-6 alkyl group]; R5 and R6 independently represent a C1-6 alkyl group: R7 represents a carboxyl group, or the like; R8, R9 and R10 independently represent a hydrogen atom, a halogen atom, or the like; and n represents an integer of 1 to 3.]

摘要翻译： 由通式（I）表示的α-苯氧基苯乙酸衍生物，其具有血管紧张素II受体拮抗作用和PPARγ活化活性，可用作高血压，代谢综合征等的预防和/或治疗剂，盐 的衍生物，或衍生物或盐的溶剂合物; 和含有该衍生物，盐或溶剂化物的药物组合物。 [式中，Q表示由式（II）或（III）表示的基团[式中，R1和R1'独立地表示C1-6烷基; R2和R2'独立地表示取代或未取代的C1-6烷基; R3表示氢原子，取代或未取代的C1-6烷基或由式（IV）表示的基团[其中X和Y独立地表示CH或N; Z表示碳原子数1〜6的亚烷基链等。 R 11表示氢原子，C 6-10芳基等; m表示0或1]; 并且R 4表示取代的C 1-6烷基]; R5和R6独立地表示C1-6烷基：R7表示羧基等; R 8，R 9和R 10独立地表示氢原子，卤素原子等; n表示1〜3的整数。

公开(公告)号：US20110306623A1

公开(公告)日：2011-12-15

申请号：US13202052

申请日：2010-02-22

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

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

IPC分类号： A61K31/506 ,  A61P3/04 ,  A61P9/12 ,  A61P3/06 ,  C07D413/14 ,  A61P3/10

CPC分类号： A61K31/513 ,  C07D403/04 ,  C07D413/14

摘要： Provided are novel compounds that have both angiotensin II receptor-antagonist effects and PPAR-activating effects that are useful as agents for preventing and/or treating hypertension, heart disease, angina, cerebral vascular accident, cerebrovascular disorder, ischemic peripheral circulatory disorder, kidney disease, atherosclerosis, inflammatory disease, type 2 diabetes mellitus, diabetic complication, insulin resistance syndrome, Syndrome X, metabolic syndrome, and hyperinsulinemia. Disclosed are 3-(5-alkoxypyrimidin-2-yl)pyrimidin-4(3H)-one derivatives represented by the General formula (I): [wherein R represents a C1-4 alkyl group], or salts or solvates thereof (I)

摘要翻译： 提供了具有血管紧张素II受体拮抗剂作用和PPAR活化作用的新型化合物，其可用作预防和/或治疗高血压，心脏病，心绞痛，脑血管意外，脑血管障碍，缺血性外周循环障碍，肾脏疾病 ，动脉粥样硬化，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。 公开了由通式（I）表示的3-（5-烷氧基嘧啶-2-基）嘧啶-4（3H） - 酮衍生物：[其中R表示C 1-4烷基]或其​​盐或溶剂合物（I ）

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.