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公开(公告)号:US20120035196A1
公开(公告)日:2012-02-09
申请号:US13265781
申请日:2010-04-21
申请人: Kenji Negoro , Kei Ohnuki , Yasuhiro Yonetoku , Kazuyuki Kuramoto , Yasuharu Urano , Hideyuki Watanabe
发明人: Kenji Negoro , Kei Ohnuki , Yasuhiro Yonetoku , Kazuyuki Kuramoto , Yasuharu Urano , Hideyuki Watanabe
IPC分类号: A61K31/505 , C07C63/36 , A61K31/216 , A61K31/192 , C07D239/34 , C07D305/06 , A61K31/337 , C07D207/46 , A61K31/4015 , C07D309/10 , A61K31/351 , C07D317/18 , A61K31/341 , A61P3/10 , C07C69/616
CPC分类号: C07D207/06 , A61K31/40 , A61K31/4015 , C07C49/417 , C07C59/68 , C07C59/72 , C07C69/732 , C07C69/734 , C07C229/42 , C07C233/18 , C07C235/20 , C07C255/37 , C07C271/30 , C07C311/04 , C07C2603/18 , C07C2603/94 , C07D207/27 , C07D239/34 , C07D305/06 , C07D307/94 , C07D309/06 , C07D309/10 , C07D317/22 , C07D319/06 , C07D405/12
摘要: [Problem]The present invention has an object to provide a compound having a GPR40 agonistic activity, which is useful as a pharmaceutical composition, an insulin secretion promoter, or an agent for preventing/treating diabetes.[Means for Solution]The present inventors have extensively studied a compound having a GPR40 agonistic activity, and as a result, they have found that the compound (I) of the present invention or a pharmaceutically acceptable salt thereof, in which a carboxylic acid is bonded to a bicyclic or tricyclic moiety through methylene, and further, a benzene ring substituted with a monocyclic 6-membered aromatic ring is bonded to a bicyclic or tricyclic moiety through —O-methylene or —NH-methylene, has an excellent GPR40 agonistic activity. They have also found that the compound has an excellent insulin secretion promoting action and strongly inhibits increase in the blood glucose after glucose loading, thereby completing the present invention.
摘要翻译: 本发明的目的是提供具有GPR40激动活性的化合物,其可用作药物组合物,胰岛素分泌促进剂或糖尿病预防/治疗剂。 [解决方案]本发明人广泛研究了具有GPR40激动活性的化合物,结果发现本发明的化合物(I)或其药学上可接受的盐,其中羧酸为 通过亚甲基键合到双环或三环部分,此外,被单环6元芳环取代的苯环通过-O-亚甲基或-NH-亚甲基与双环或三环部分连接,具有优异的GPR40激动活性 。 他们还发现该化合物具有优异的胰岛素分泌促进作用,并且强烈地抑制葡萄糖负荷后血糖的增加,从而完成本发明。
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公开(公告)号:US07968552B2
公开(公告)日:2011-06-28
申请号:US12298522
申请日:2007-04-23
申请人: Kenji Negoro , Fumiyoshi Iwasaki , Kei Ohnuki , Toshio Kurosaki , Yasuhiro Yonetoku , Norio Asai , Shigeru Yoshida , Takatoshi Soga
发明人: Kenji Negoro , Fumiyoshi Iwasaki , Kei Ohnuki , Toshio Kurosaki , Yasuhiro Yonetoku , Norio Asai , Shigeru Yoshida , Takatoshi Soga
IPC分类号: A61K31/506 , A61K31/4439 , A61K31/4245 , C07D413/12 , C07D271/07
CPC分类号: C07D271/06 , C07D271/07 , C07D413/12 , C07D413/14 , C07D417/12 , C07D417/14
摘要: A compound which can be used as a pharmaceutical, particularly a insulin secretion promoter or a agent for preventing/treating disease in which GPR40 is concerned such as diabetes or the like, is provided.It was found that an oxadiazolidinedione compound which is characterized by the possession of a benzyl or the like substituent binding to the cyclic group via a linker at the 2-position of the oxadiazolidinedione ring, or a pharmaceutically acceptable salt thereof, has excellent GPR40 agonist action. In addition, since the oxadiazolidinedione compound of the present invention showed excellent insulin secretion promoting action and blood glucose level-lowering action, it is useful as an insulin secretion promoter or an agent for preventing/treating diabetes.
摘要翻译: 可以提供可用作药物的化合物,特别是胰岛素分泌促进剂或用于预防/治疗其中涉及GPR40的疾病如糖尿病等的化合物。 已经发现,具有通过在恶二唑烷二酮环2位上的连接体与环状基团结合的苄基等取代基的恶二唑烷二酮化合物或其药学上可接受的盐具有优异的GPR40激动剂作用 。 此外,由于本发明的恶二唑烷二酮化合物显示出优异的胰岛素分泌促进作用和血糖降低作用,因此可用作胰岛素分泌促进剂或糖尿病的预防/治疗剂。
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公开(公告)号:US20100152165A1
公开(公告)日:2010-06-17
申请号:US12517033
申请日:2007-11-29
申请人: Kenji Negoro , Kei Ohnuki , Toshio Kurosaki , Fumiyoshi Iwasaki , Yasuhiro Yonetoku , Kazuyuki Tsuchiya , Norio Asai , Shigeru Yoshida , Takatoshi Soga , Daisuke Suzuki
发明人: Kenji Negoro , Kei Ohnuki , Toshio Kurosaki , Fumiyoshi Iwasaki , Yasuhiro Yonetoku , Kazuyuki Tsuchiya , Norio Asai , Shigeru Yoshida , Takatoshi Soga , Daisuke Suzuki
IPC分类号: A61K31/55 , C07D215/20 , A61K31/47 , C07D223/16 , C07D279/16 , A61K31/5415 , A61K31/4375 , C07D471/02
CPC分类号: C07D471/04 , C07D209/08 , C07D215/12 , C07D215/14 , C07D215/20 , C07D215/227 , C07D215/26 , C07D215/38 , C07D215/40 , C07D215/58 , C07D265/36 , C07D279/16 , C07D401/04 , C07D401/06 , C07D401/10 , C07D401/12 , C07D403/12 , C07D405/06 , C07D405/12 , C07D409/06 , C07D413/12
摘要: [Problem] To provide a pharmaceutical, particularly a compound which can be used as an insulin secretion promoter or a preventive or therapeutic agent for diabetes mellitus and the like diseases in which GPR40 is concerned.[Means for resolution] It was found that novel carboxylic acid derivatives or salts thereof, characterized in that carboxylic acid is linked to a 6-membered monocyclic aromatic ring via two atoms and said aromatic ring is linked to a nitrogen-containing bicyclic ring via a linker, have excellent GPR40 receptor agonist action. In addition, since the carboxylic acid derivatives of the invention showed excellent insulin secretion promoting action and blood glucose reducing action, they are useful as an insulin secretion promoter and a preventive or therapeutic agent for diabetes mellitus.
摘要翻译: [问题]提供可以用作胰岛素分泌促进剂的药物,特别是涉及GPR40的糖尿病等的预防或治疗剂的化合物。 [解决方法]发现新的羧酸衍生物或其盐,其特征在于羧酸通过两个原子与6元单环芳香环连接,所述芳环经由含氮双环通过 接头,具有优异的GPR40受体激动作用。 此外,由于本发明的羧酸衍生物显示出优异的胰岛素分泌促进作用和降血糖作用,因此它们可用作糖尿病的胰岛素分泌促进剂和预防或治疗剂。
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公开(公告)号:US20090186909A1
公开(公告)日:2009-07-23
申请号:US12298522
申请日:2007-04-23
申请人: Kenji Negoro , Fumiyoshi Iwasaki , Kei Ohnuki , Toshio Kurosaki , Yasuhiro Yonetoku , Norio Asai , Shigeru Yoshida , Takatoshi Soga
发明人: Kenji Negoro , Fumiyoshi Iwasaki , Kei Ohnuki , Toshio Kurosaki , Yasuhiro Yonetoku , Norio Asai , Shigeru Yoshida , Takatoshi Soga
IPC分类号: A61K31/506 , A61K31/4439 , A61K31/4245 , C07D413/12 , C07D271/07
CPC分类号: C07D271/06 , C07D271/07 , C07D413/12 , C07D413/14 , C07D417/12 , C07D417/14
摘要: [Problem] A compound which can be used as a pharmaceutical, particularly a insulin secretion promoter or a agent for preventing/treating disease in which GPR40 is concerned such as diabetes or the like, is provided.[Means for resolution] It was found that an oxadiazolidinedione compound which is characterized by the possession of a benzyl or the like substituent binding to the cyclic group via a linker at the 2-position of the oxadiazolidinedione ring, or a pharmaceutically acceptable salt thereof, has excellent GPR40 agonist action. In addition, since the oxadiazolidinedione compound of the present invention showed excellent insulin secretion promoting action and blood glucose level-lowering action, it is useful as an insulin secretion promoter or an agent for preventing/treating diabetes.
摘要翻译: 可以提供可用作药物的化合物,特别是胰岛素分泌促进剂或用于预防/治疗其中涉及GPR40的疾病如糖尿病等的化合物。 [解决方法]已经发现,恶二唑烷二酮化合物或其药学上可接受的盐,其特征在于具有通过在恶二唑烷二酮环的2位上的连接基与环状基团结合的苄基等取代基, 具有优异的GPR40激动作用。 此外,由于本发明的恶二唑烷二酮化合物显示出优异的胰岛素分泌促进作用和血糖降低作用,因此可用作胰岛素分泌促进剂或糖尿病的预防/治疗剂。
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公开(公告)号:US20100267775A1
公开(公告)日:2010-10-21
申请号:US12739501
申请日:2008-10-22
申请人: Kenji Negoro , Fumiyoshi Iwasaki , Kei Ohnuki , Toshio Kurosaki , Kazuyuki Tsuchiya , Kazuyuki Kuramoto , Shigeru Yoshida , Takatoshi Soga
发明人: Kenji Negoro , Fumiyoshi Iwasaki , Kei Ohnuki , Toshio Kurosaki , Kazuyuki Tsuchiya , Kazuyuki Kuramoto , Shigeru Yoshida , Takatoshi Soga
IPC分类号: A61K31/4439 , C07D271/07 , A61K31/4245 , A61P3/10 , C07D413/12
CPC分类号: C07D271/06 , C07D271/07 , C07D413/12
摘要: A pharmaceutical agent having GPR40 receptor agonistic action, particularly a compound which is useful as an insulin secretagogue or an agent for preventing and/or treating diabetes mellitus. The present inventors have examined a compound having GPR40 receptor agonistic action, confirmed that an oxadiazolidinedione compound which has a substituent such as a benzyl group, etc. linked with a substituent such as a phenyl group, etc. through a linker at the 2-position of an oxadiazolidinedione ring, or a pharmaceutically acceptable salt thereof has an excellent GPR40 agonistic activity, and thus completed the invention. The oxadiazolidinedione compound has excellent insulin secretagogue action and anti-hyperglycemic action, and therefore can be used as an insulin secretagogue or an agent for preventing and/or treating diabetes mellitus.
摘要翻译: 具有GPR40受体激动作用的药剂,特别是可用作胰岛素促分泌剂的化合物或用于预防和/或治疗糖尿病的药剂。 本发明人已经研究了具有GPR40受体激动作用的化合物,证实了通过2-位的连接基与诸如苯基等取代基连接的具有苄基等取代基的恶二唑烷二酮化合物等 的恶二唑烷二酮环或其药学上可接受的盐具有优异的GPR40激动活性,从而完成了本发明。 恶二唑烷二酮化合物具有优异的胰岛素促分泌作用和抗高血糖作用,因此可用作胰岛素促分泌素或预防和/或治疗糖尿病的药剂。
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公开(公告)号:US20070249587A1
公开(公告)日:2007-10-25
申请号:US11576889
申请日:2005-10-05
申请人: Yasuhiro Yonetoku , Kenji Negoro , Kenichi Onda , Masahiko Hayakawa , Daisuke Sasuga , Takahiro Nigawara , Kazuhiko Iikubo , Hiroyuki Moritomo , Shigeru Yoshida , Takahide Ohishi
发明人: Yasuhiro Yonetoku , Kenji Negoro , Kenichi Onda , Masahiko Hayakawa , Daisuke Sasuga , Takahiro Nigawara , Kazuhiko Iikubo , Hiroyuki Moritomo , Shigeru Yoshida , Takahide Ohishi
IPC分类号: A61K31/517 , A61K31/519 , A61K31/55 , A61P3/10 , C07D403/02 , C07D471/04 , C07D495/04
CPC分类号: C07D471/04 , C07D495/04 , C07D513/04
摘要: There are provided novel pyrimidine derivatives which has been fused with an aromatic heterocycle selected from thiophene, thiazole and pyridine or pharmaceutically acceptable salts thereof; and a pharmaceutical composition comprising said compound as an active ingredient. These compounds exhibit excellent promoting activity on insulin secretion and activity against hyperglycemia. Hence, the pharmaceutical compositions comprising such compounds as active ingredients, based on these actions, are useful for treating and/or preventing insulin-dependent diabetes (type 1 diabetes), non-insulin-dependent diabetes (type 2 diabetes), insulin-resistant diseases, obesity, and the like.
摘要翻译: 提供已经与选自噻吩,噻唑和吡啶的芳族杂环或其药学上可接受的盐融合的新的嘧啶衍生物; 以及包含所述化合物作为活性成分的药物组合物。 这些化合物对胰岛素分泌表现出优异的促进活性和抗高血糖的活性。 因此,基于这些作用,包含这些化合物作为活性成分的药物组合物可用于治疗和/或预防胰岛素依赖性糖尿病(1型糖尿病),非胰岛素依赖性糖尿病(2型糖尿病),胰岛素抵抗 疾病,肥胖等。
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公开(公告)号:US07557112B2
公开(公告)日:2009-07-07
申请号:US11576889
申请日:2005-10-05
申请人: Yasuhiro Yonetoku , Kenji Negoro , Kenichi Onda , Masahiko Hayakawa , Daisuke Sasuga , Takahiro Nigawara , Kazuhiko Iikubo , Hiroyuki Moritomo , Shigeru Yoshida , Takahide Ohishi
发明人: Yasuhiro Yonetoku , Kenji Negoro , Kenichi Onda , Masahiko Hayakawa , Daisuke Sasuga , Takahiro Nigawara , Kazuhiko Iikubo , Hiroyuki Moritomo , Shigeru Yoshida , Takahide Ohishi
IPC分类号: A61P3/10 , C07D495/04 , C07D279/12 , C07D417/04 , C07D413/04 , A61K31/541 , A61K31/5355 , A61K31/519
CPC分类号: C07D471/04 , C07D495/04 , C07D513/04
摘要: There are provided novel pyrimidine derivatives which has been fused with an aromatic heterocycle selected from thiophene, thiazole and pyridine or pharmaceutically acceptable salts thereof; and a pharmaceutical composition comprising said compound as an active ingredient. These compounds exhibit excellent promoting activity on insulin secretion and activity against hyperglycemia. Hence, the pharmaceutical compositions comprising such compounds as active ingredients, based on these actions, are useful for treating and/or preventing insulin-dependent diabetes (type 1 diabetes), non-insulin-dependent diabetes (type 2 diabetes), insulin-resistant diseases, obesity, and the like.
摘要翻译: 提供已经与选自噻吩,噻唑和吡啶的芳族杂环或其药学上可接受的盐融合的新的嘧啶衍生物; 以及包含所述化合物作为活性成分的药物组合物。 这些化合物对胰岛素分泌表现出优异的促进活性和抗高血糖的活性。 因此,基于这些作用,包含这些化合物作为活性成分的药物组合物可用于治疗和/或预防胰岛素依赖性糖尿病(1型糖尿病),非胰岛素依赖型糖尿病(2型糖尿病),胰岛素抵抗 疾病,肥胖等。
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公开(公告)号:US07947690B2
公开(公告)日:2011-05-24
申请号:US11577648
申请日:2005-10-17
申请人: Yasuhiro Yonetoku , Kenji Negoro , Kenichi Onda , Masahiko Hayakawa , Daisuke Sasuga , Takahiro Nigawara , Kazuhiko Iikubo , Hiroyuki Moritomo , Shigeru Yoshida , Takahide Ohishi
发明人: Yasuhiro Yonetoku , Kenji Negoro , Kenichi Onda , Masahiko Hayakawa , Daisuke Sasuga , Takahiro Nigawara , Kazuhiko Iikubo , Hiroyuki Moritomo , Shigeru Yoshida , Takahide Ohishi
IPC分类号: A61K31/519 , A61K31/497 , C07D495/04 , A61P3/10 , C07D487/04 , C07D471/04 , C07D239/72 , A61K31/517
CPC分类号: C07D239/70 , C07D239/94 , C07D495/04
摘要: The present invention provides a condensed pyrimidine compound represented by formula (I) or pharmaceutically acceptable salt thereof: where A represents a ring where at least one carbon atom within said ring is optionally substituted with one or more groups selected from the group consisting of lower alkyl, —O-(lower alkyl), halogen atom, carboxyl, —CO2-(lower alkyl), and carbamoyl, R1 represents: (1) phenyl substituted with at least three halogen atoms, which may have at least one additional substituent, or (2) cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, each of which is optionally substituted; and R2 represents a group represented by formula (II) or an optionally substituted cyclic amino: wherein R21 and R22 may be identical or different and each represents —H, lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, phenyl, heteroaryl, non-aromatic heterocyclyl, or —O-(lower alkyl), each of which is optionally substituted.
摘要翻译: 本发明提供由式(I)表示的稠合嘧啶化合物或其药学上可接受的盐:其中A表示环,其中所述环中至少一个碳原子任选被一个或多个选自以下的基团取代:低级烷基 ,-O-(低级烷基),卤素原子,羧基,-CO 2 - (低级烷基)和氨基甲酰基,R 1表示:(1)被至少三个卤素原子取代的苯基,其可以具有至少一个另外的取代基,或 (2)环丙基,环丁基,环戊基,环己基或环庚基,其各自任选被取代; 并且R 2表示由式(II)表示的基团或任选取代的环状氨基:其中R 21和R 22可以相同或不同,并且各自表示-H,低级烷基,低级烯基,低级炔基,环烷基,苯基,杂芳基, 芳族杂环基或-O-(低级烷基),其各自任选被取代。
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公开(公告)号:US20080070896A1
公开(公告)日:2008-03-20
申请号:US11577648
申请日:2005-10-17
申请人: Yasuhiro Yonetoku , Kenji Negoro , Kenichi Onda , Masahiko Hayakawa , Daisuke Sasuga , Takahiro Nigawara , Kazuhiko Iikubo , Hiroyuki Moritomo , Shigeru Yoshida , Takahide Ohishi
发明人: Yasuhiro Yonetoku , Kenji Negoro , Kenichi Onda , Masahiko Hayakawa , Daisuke Sasuga , Takahiro Nigawara , Kazuhiko Iikubo , Hiroyuki Moritomo , Shigeru Yoshida , Takahide Ohishi
IPC分类号: A61K31/519 , A61K31/497 , A61K31/5377 , A61K31/551 , A61P3/00 , C07D285/36 , C07D413/14 , C07D495/04 , C07D487/04 , C07D403/04 , C07D239/70 , A61K31/554 , A61K31/55 , A61K31/517
CPC分类号: C07D239/70 , C07D239/94 , C07D495/04
摘要: There are provided new pyrimidine derivatives condensed with a non-aromatic ring selected from dihydrothiophene, dihydrofuran, cycloalkane moiety, and the like or pharmaceutically acceptable salts thereof; and a pharmaceutical composition comprising said compound as an active ingredient. These compounds exhibit excellent promoting activity on insulin secretion and activity against hyperglycemia. Hence, the pharmaceutical compositions comprising such compounds as active ingredients, based on these actions, are useful for treating and/or preventing insulin-dependent diabetes (type 1 diabetes), non-insulin-dependent diabetes (type 2 diabetes), insulin-resistant diseases, obesity, and the like.
摘要翻译: 提供了与选自二氢噻吩,二氢呋喃,环烷烃部分等的非芳香环稠合的新的嘧啶衍生物或其药学上可接受的盐; 以及包含所述化合物作为活性成分的药物组合物。 这些化合物对胰岛素分泌表现出优异的促进活性和抗高血糖的活性。 因此,基于这些作用,包含这些化合物作为活性成分的药物组合物可用于治疗和/或预防胰岛素依赖性糖尿病(1型糖尿病),非胰岛素依赖性糖尿病(2型糖尿病),胰岛素抵抗 疾病,肥胖等。
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公开(公告)号:US08022208B2
公开(公告)日:2011-09-20
申请号:US12091099
申请日:2006-11-07
申请人: Fukushi Hirayama , Jiro Fujiyasu , Daisuke Kaga , Kenji Negoro , Daisuke Sasuga , Norio Seki , Ken-ichi Suzuki
发明人: Fukushi Hirayama , Jiro Fujiyasu , Daisuke Kaga , Kenji Negoro , Daisuke Sasuga , Norio Seki , Ken-ichi Suzuki
IPC分类号: C07D419/14 , C07D279/12 , C07D401/14 , C07D211/94 , C07D213/62 , C07D267/10 , A61K31/553 , A61K31/554 , A61K31/546 , A61K31/5355 , A61K31/497 , A61K31/445 , A61K31/444
CPC分类号: C07D213/75 , C07D211/76 , C07D213/64 , C07D239/36 , C07D241/18 , C07D401/12 , C07D401/14 , C07D405/12 , C07D405/14 , C07D409/12 , C07D409/14 , C07D413/14 , C07D417/14
摘要: Problem: To provide compounds which have an anticoagulation effect based on their ability to inhibit the activated blood coagulation factor X and are useful as coagulation inhibitors or agents for prevention or treatment for diseases caused by thrombi or emboli.Means for Solution: Benzene derivatives or their salts having a characteristic chemical structure with a phenol ring and a benzene ring bonding to each other via an amide bond, in which the phenol ring further bonds to a benzene ring or a heteroaryl ring via an amide bond. They have an excellent effect of inhibiting the activated blood coagulation factor X, and especially have an excellent oral activity.
摘要翻译: 问题:提供基于其抑制活化凝血因子X的能力具有抗凝作用的化合物,并且可用作凝血抑制剂或用于预防或治疗由血栓或栓塞引起的疾病的药剂。 解决方法:苯衍生物或其具有特征化学结构的苯酚环和苯环通过酰胺键彼此键合,其中酚环还通过酰胺键与苯环或杂芳基环键合 。 它们具有抑制活化凝血因子X的优异效果,特别是具有优异的口服活性。
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