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1. 发明授权

US06630463B2 Heterocycle-containing carboxylic acid derivative and drug containing the same 失效
标题翻译：含有杂环的羧酸衍生物和含有它们的药物
公开(公告)号：US06630463B2
公开(公告)日：2003-10-07
申请号：US09910068
申请日：2001-07-23
申请人： Kouichi Kikuchi , Katsuya Tagami , Hiroyuki Yoshimura , Shigeki Hibi , Mitsuo Nagai , Shinya Abe , Makoto Okita , Takayuki Hida , Seiko Higashi , Naoki Tokuhara , Seiichi Kobayashi
发明人： Kouichi Kikuchi , Katsuya Tagami , Hiroyuki Yoshimura , Shigeki Hibi , Mitsuo Nagai , Shinya Abe , Makoto Okita , Takayuki Hida , Seiko Higashi , Naoki Tokuhara , Seiichi Kobayashi
IPC分类号： A61K31404
CPC分类号： C07D401/04 , C07D209/14 , C07D231/12 , C07D241/24 , C07D241/44 , C07D249/10 , C07D401/14 , C07D403/04 , C07D405/04 , C07D407/04 , C07D409/04 , C07D413/04 , C07D417/04 , C07D471/04
摘要： Described is a heterocycle-containing carboxylic acid derivative represented by the following formula (I): wherein A represents, for example, a heteroaryl group which contains at least one nitrogen atom and may have a substituent, B represents, for example, a heteroarylene group, a —CONH— group or a group represented by the formula —CR6═CR7— in which R6 and R7 represents H, a lower alkyl group or the like, D represents an arylene group, a heteroarylene group or the like, n1 stands for 0 or 1, M represents, for example, a hydroxyl group or a lower alkoxy group; or a physiologically acceptable salt thereof. As a retinoic-related compound replacing retinoic acid, it permits the provision of a preventive and/or therapeutic for various diseases.
摘要翻译：描述了由下式（I）表示的含杂环羧酸衍生物：其中A表示例如含有至少一个氮原子并且可以具有取代基的杂芳基，B表示例如亚杂芳基 -CONH-基或由式-CR 6 = CR 7表示的基团，其中R 6和R 7表示H，低级烷基等，D表示亚芳基基团，亚杂芳基等，n1表示0或1，M表示例如羟基或低级烷氧基; 或其生理上可接受的盐。作为视黄酸相关化合物代替视黄酸，它允许为各种疾病提供预防和/或治疗。

2. 发明授权

US06541474B2 Heterocycle-containing carboxylic acid derivative and drug containing the same 失效
标题翻译：含有杂环的羧酸衍生物和含有它们的药物
公开(公告)号：US06541474B2
公开(公告)日：2003-04-01
申请号：US09910012
申请日：2001-07-23
申请人： Kouichi Kikuchi , Katsuya Tagami , Hiroyuki Yoshimura , Shigeki Hibi , Mitsuo Nagai , Shinya Abe , Makoto Okita , Takayuki Hida , Seiko Higashi , Naoki Tokuhara , Seiichi Kobayashi
发明人： Kouichi Kikuchi , Katsuya Tagami , Hiroyuki Yoshimura , Shigeki Hibi , Mitsuo Nagai , Shinya Abe , Makoto Okita , Takayuki Hida , Seiko Higashi , Naoki Tokuhara , Seiichi Kobayashi
IPC分类号： A61K314965
CPC分类号： C07D401/04 , C07D209/14 , C07D231/12 , C07D241/24 , C07D241/44 , C07D249/10 , C07D401/14 , C07D403/04 , C07D405/04 , C07D407/04 , C07D409/04 , C07D413/04 , C07D417/04 , C07D471/04
摘要： Described is a heterocycle-containing carboxylic acid derivative represented by the following formula (I): wherein A represents, for example, a heteroaryl group which contains at least one nitrogen atom and may have a substituent, B represents, for example, a heteroarylene group, a —CONH— group or a group represented by the formula —CR6═CR7— in which R6 and R7 represents H, a lower alkyl group or the like, D represents an arylene group, a heteroarylene group or the like, n1 stands for 0 or 1, M represents, for example, a hydroxyl group or a lower alkoxy group; or a physiologically acceptable salt thereof. As a retinoic-related compound replacing retinoic acid, it permits the provision of a preventive and/or therapeutic for various diseases.
摘要翻译：描述了由下式（I）表示的含杂环羧酸衍生物：其中A表示例如含有至少一个氮原子并且可以具有取代基的杂芳基，B表示例如亚杂芳基 -CONH-基或由式-CR 6 = CR 7 - 表示的基团，其中R 6和R 7表示H，低级烷基等，D表示亚芳基，亚杂芳基等，n1表示 0或1，M表示例如羟基或低级烷氧基; 或其生理上可接受的盐。作为视黄酸相关化合物代替视黄酸，它允许为各种疾病提供预防和/或治疗。

3. 发明授权

US06329402B1 Heterocycle-containing carboxylic acid derivative and drug containing the same 失效
标题翻译：含有杂环的羧酸衍生物和含有它们的药物
公开(公告)号：US06329402B1
公开(公告)日：2001-12-11
申请号：US09313087
申请日：1999-05-17
申请人： Kouichi Kikuchi , Katsuya Tagami , Hiroyuki Yoshimura , Shigeki Hibi , Mitsuo Nagai , Shinya Abe , Makoto Okita , Takayuki Hida , Seiko Higashi , Naoki Tokuhara , Seiichi Kobayashi
发明人： Kouichi Kikuchi , Katsuya Tagami , Hiroyuki Yoshimura , Shigeki Hibi , Mitsuo Nagai , Shinya Abe , Makoto Okita , Takayuki Hida , Seiko Higashi , Naoki Tokuhara , Seiichi Kobayashi
IPC分类号： A61K31415
CPC分类号： C07D401/04 , C07D209/14 , C07D231/12 , C07D241/24 , C07D241/44 , C07D249/10 , C07D401/14 , C07D403/04 , C07D405/04 , C07D407/04 , C07D409/04 , C07D413/04 , C07D417/04 , C07D471/04
摘要： Described is a heterocycle-containing carboxylic acid derivative represented by the following formula (I): wherein A represents, for example, a heteroaryl group which contains at least one nitrogen atom and may have a substituent, B represents, for example, a heteroarylene group, a —CONH— group or a group represented by the formula —CR6═CR7— in which R6 and R7 represents H, a lower alkyl group or the like, D represents an arylene group, a heteroarylene group or the like, n1 stands for 0 or 1, M represents, for example, a hydroxyl group or a lower alkoxy group; or a physiologically acceptable salt thereof. As a retinoic-related compound replacing retinoic acid, it permits the provision of a preventive and/or therapeutic for various diseases.
摘要翻译：描述了由下式（I）表示的含杂环羧酸衍生物：其中A表示例如含有至少一个氮原子并且可以具有取代基的杂芳基，B表示例如亚杂芳基 -CONH-基或由式-CR 6 = CR 7 - 表示的基团，其中R 6和R 7表示H，低级烷基等，D表示亚芳基，亚杂芳基等，n1表示 0或1，M表示例如羟基或低级烷氧基; 或其生理上可接受的盐。作为视黄酸相关化合物代替视黄酸，它允许为各种疾病提供预防和/或治疗。

4. 发明授权

US5977108A Heterocycle-containing carboxylic acid derivative and drug containing the same 失效
标题翻译：含有杂环的羧酸衍生物和含有它们的药物
公开(公告)号：US5977108A
公开(公告)日：1999-11-02
申请号：US981770
申请日：1997-12-30
申请人： Kouichi Kikuchi , Katsuya Tagami , Hiroyuki Yoshimura , Shigeki Hibi , Mitsuo Nagai , Shinya Abe , Makoto Okita , Takayuki Hida , Seiko Higashi , Naoki Tokuhara , Seiichi Kobayashi
发明人： Kouichi Kikuchi , Katsuya Tagami , Hiroyuki Yoshimura , Shigeki Hibi , Mitsuo Nagai , Shinya Abe , Makoto Okita , Takayuki Hida , Seiko Higashi , Naoki Tokuhara , Seiichi Kobayashi
IPC分类号： C07D253/06 , A61K31/40 , A61K31/403 , A61K31/404 , A61K31/415 , A61K31/44 , A61K31/4409 , A61K31/4418 , A61K31/4427 , A61K31/443 , A61K31/4433 , A61K31/47 , A61K31/495 , A61K31/53 , A61K31/535 , A61P1/16 , A61P11/00 , A61P17/00 , A61P29/00 , A61P31/04 , A61P35/00 , A61P35/02 , A61P37/06 , A61P37/08 , A61P43/00 , C07D209/14 , C07D213/82 , C07D215/22 , C07D231/12 , C07D233/66 , C07D241/24 , C07D241/38 , C07D241/44 , C07D241/46 , C07D249/10 , C07D401/04 , C07D401/14 , C07D403/04 , C07D405/04 , C07D405/06 , C07D405/14 , C07D407/04 , C07D409/04 , C07D413/04 , C07D417/04 , C07D471/04 , C07D495/04 , C10J3/00
CPC分类号： C07D401/04 , C07D209/14 , C07D231/12 , C07D241/24 , C07D241/44 , C07D249/10 , C07D401/14 , C07D403/04 , C07D405/04 , C07D407/04 , C07D409/04 , C07D413/04 , C07D417/04 , C07D471/04
摘要： Described is a heterocycle-containing carboxylic acid derivative represented by the following formula (I): ##STR1## wherein A represents, for example, a heteroaryl group which contains at least one nitrogen atom and may have a substituent, B represents, for example, a heteroarylene group, a --CONH-- group or a group represented by the formula --CR.sup.6 .dbd.CR.sup.7 -- in which R.sup.6 and R.sup.7 represents H, a lower alkyl group or the like, D represents an arylene group, a heteroarylene group or the like, n1 stands for 0 or 1, M represents, for example, a hydroxyl group or a lower alkoxy group; or a physiologically acceptable salt thereof. As a retinoic-related compound replacing retinoic acid, it permits the provision of a preventive and/or therapeutic for various diseases.
摘要翻译： PCT No.PCT / JP96 / 01782 Sec。 371日期1997年12月30日 102（e）1997年12月30日PCT PCT 1996年6月27日PCT公布。出版物WO97 / 02244 日期1997年1月23日描述了由下式（I）表示的含杂环羧酸衍生物：其中A表示例如含有至少一个氮原子并可以具有取代基的杂芳基，B表示例如，亚杂芳基，-CONH-基或由式-CR 6 = CR 7 - 表示的基团，其中R 6和R 7表示H，低级烷基等，D表示亚芳基，亚杂芳基或 n1表示0或1，M表示例如羟基或低级烷氧基; 或其生理上可接受的盐。作为视黄酸相关化合物代替视黄酸，它允许为各种疾病提供预防和/或治疗。

5. 发明授权

US6110959A Carboxylic acid derivatives having fused rings 失效
标题翻译：具有稠环的羧酸衍生物
公开(公告)号：US6110959A
公开(公告)日：2000-08-29
申请号：US400980
申请日：1999-09-22
申请人： Katsuya Tagami , Hiroyuki Yoshimura , Mitsuo Nagai , Shigeki Hibi , Kouichi Kikuchi , Takashi Sato , Makoto Okita , Yasushi Okamoto , Yumiko Nagasaka , Naoki Kobayashi , Takayuki Hida , Kenji Tai , Naoki Tokuhara , Seiichi Kobayashi
发明人： Katsuya Tagami , Hiroyuki Yoshimura , Mitsuo Nagai , Shigeki Hibi , Kouichi Kikuchi , Takashi Sato , Makoto Okita , Yasushi Okamoto , Yumiko Nagasaka , Naoki Kobayashi , Takayuki Hida , Kenji Tai , Naoki Tokuhara , Seiichi Kobayashi
IPC分类号： C07C69/76 , C07C69/94 , C07D207/32 , C07D207/337 , C07D307/54 , C07D333/24 , C07D405/04 , C07D405/10 , C07D405/14 , C07D407/04 , C07D409/04 , C07D409/10 , C07D409/14 , A61K31/40 , C07D207/30
CPC分类号： C07D207/337 , C07C69/76 , C07C69/94 , C07D307/54 , C07D333/24 , C07D405/04 , C07D405/10 , C07D405/14 , C07D407/04 , C07D409/04 , C07D409/10 , C07D409/14
摘要： The present invention provides a medicament exhibiting excellent retinoic acid receptor agonism.A Carboxylic acid derivative having a fused ring which is represented by the following formula or a pharmacologically acceptable salt thereof: ##STR1## {wherein the symbol ##STR2## represents a single bond or a double bond; X, Y, Z, P, Q, U, V and W are each a group represented by the formula: --O-- or --S--, or a group represented by the formula: ##STR3## [wherein R.sup.k (k: 1 to 8) is hydrogen, halogeno, optionally substituted lower alkyl or the like, with either of R.sup.7 and R.sup.8 being a group represented by the formula: ##STR4## (wherein A and B are each independently an optionally substituted aromatic hydrocarbon ring or an optionally substituted unsaturated heterocycle; and D is optionally protected carboxyl)]}.
摘要翻译：本发明提供了显示出优异的视黄酸受体激动作用的药物。具有由下式表示的稠环的羧酸衍生物或其药理学上可接受的盐：其中符号表示单键或双键; X，Y，Z，P，Q，U，V和W分别是由下式表示的基团：-O-或-S-，或由下式表示的基团：[其中R k（k：1至8）是氢，卤素，任选取代的低级烷基等，其中R 7和R 8中的任一个是由下式表示的基团：（其中A和B各自独立地是任选取代的芳族烃环或任选取代的不饱和杂环; D 任选保护羧基）]}。

6. 发明授权

US6121309A Fused-ring carboxylic acid derivatives 失效
标题翻译：稠环羧酸衍生物
公开(公告)号：US6121309A
公开(公告)日：2000-09-19
申请号：US125522
申请日：1998-08-20
申请人： Katsuya Tagami , Hiroyuki Yoshimura , Mitsuo Nagai , Shigeki Hibi , Kouichi Kikuchi , Takashi Sato , Makoto Okita , Yasushi Okamoto , Yumiko Nagasaka , Naoki Kobayashi , Takayuki Hida , Kenji Tai , Naoki Tokuhara , Seiichi Kobayashi
发明人： Katsuya Tagami , Hiroyuki Yoshimura , Mitsuo Nagai , Shigeki Hibi , Kouichi Kikuchi , Takashi Sato , Makoto Okita , Yasushi Okamoto , Yumiko Nagasaka , Naoki Kobayashi , Takayuki Hida , Kenji Tai , Naoki Tokuhara , Seiichi Kobayashi
IPC分类号： C07C69/76 , C07C69/94 , C07D207/32 , C07D207/337 , C07D307/54 , C07D333/24 , C07D405/04 , C07D405/10 , C07D405/14 , C07D407/04 , C07D409/04 , C07D409/10 , C07D409/14 , A61K31/40 , C07D405/00
CPC分类号： C07D207/337 , C07C69/76 , C07C69/94 , C07D307/54 , C07D333/24 , C07D405/04 , C07D405/10 , C07D405/14 , C07D407/04 , C07D409/04 , C07D409/10 , C07D409/14
摘要： The present invention provides a medicament exhibiting excellent retinoic acid receptor agonism.A Carboxylic acid derivative having a fused ring which is represented by the following formula or a pharmacologically acceptable salt thereof: ##STR1## {wherein the symbol ----- represents a single bond or a double bond; X, Y, Z, P, Q, U, V and W are each a group represented by the formula: --O-- or --S--, or a group represented by the formula: ##STR2## [wherein R.sup.k (k:1 to 8) is hydrogen, halogeno, optionally substituted lower alkyl or the like, with either of R.sup.7 and R.sup.8 being a group represented by the formula: ##STR3## (wherein A and B are each independently an optionally substituted aromatic hydrocarbon ring or an optionally substituted unsaturated heterocycle; and D is optionally protected carboxyl)]}.
摘要翻译： PCT No.PCT / JP97 / 00852 Sec。 371日期：1998年8月20日 102（e）1998年8月20日PCT PCT 1997年3月18日PCT公布。公开号WO97 / 34869 日期：1997年9月25日本发明提供了显示出优异的视黄酸受体激动作用的药物。具有由下式表示的稠环的羧酸衍生物或其药理学上可接受的盐：{其中符号+ E，uns ----- + EE表示单键或双键; X，Y，Z，P，Q，U，V和W分别是由下式表示的基团：-O-或-S-，或由下式表示的基团：[其中R k（k：1至8）是氢，卤素，任选取代的低级烷基等，其中R 7和R 8中的任一个是由下式表示的基团：（其中A和B各自独立地是任选取代的芳族烃环或任选取代的不饱和杂环; D 任选保护羧基）]}。

7. 发明授权

US06358995B1 Carboxylic acid derivatives having fused rings 失效
标题翻译：具有稠环的羧酸衍生物
公开(公告)号：US06358995B1
公开(公告)日：2002-03-19
申请号：US09621889
申请日：2000-07-21
申请人： Katsuya Tagami , Hiroyuki Yoshimura , Mitsuo Nagai , Shigeki Hibi , Kouichi Kikuchi , Takashi Sato , Makoto Okita , Yasushi Okamoto , Yumiko Nagasaka , Naoki Kobayashi , Takayuki Hida , Kenji Tai , Naoki Tokuhara , Seiichi Kobayashi
发明人： Katsuya Tagami , Hiroyuki Yoshimura , Mitsuo Nagai , Shigeki Hibi , Kouichi Kikuchi , Takashi Sato , Makoto Okita , Yasushi Okamoto , Yumiko Nagasaka , Naoki Kobayashi , Takayuki Hida , Kenji Tai , Naoki Tokuhara , Seiichi Kobayashi
IPC分类号： A61K3140
CPC分类号： C07D207/337 , C07C69/76 , C07C69/94 , C07D307/54 , C07D333/24 , C07D405/04 , C07D405/10 , C07D405/14 , C07D407/04 , C07D409/04 , C07D409/10 , C07D409/14
摘要： The present invention provides a medicament exhibiting excellent retinoic acid receptor agonism. A Carboxylic acid derivative having a fused ring which is represented by the following formula or a pharmacologically acceptable salt thereof: {wherein the symbol represents a single bond or a double bond; X, Y, Z, P, Q, U, V and W are each a group represented by the formula: —O— or —S—, or a group represented by the formula: [wherein Rk (k: 1 to 8) is hydrogen, halogeno, optionally substituted lower alkyl or the like, with either of R7 and R8 being a group represented by the formula: (wherein A and B are each independently an optionally substituted aromatic hydrocarbon ring or an optionally substituted unsaturated heterocycle; and D is optionally protected carboxyl)]}.
摘要翻译：本发明提供一种显示出优异的视黄酸受体激动作用的药物。具有下式表示的稠环的羧酸衍生物或其药理学上可接受的盐：{其中符号表示单键或双键; X，Y，Z，P，Q，U，V和W分别是由下式表示的基团：-O-或-S-，或由下式表示的基团：[其中R k（k：1至8）是氢，卤素，任选取代的低级烷基等，其中R 7和R 8中的任一个是由下式表示的基团：（其中A和B各自独立地是任选取代的芳族烃环或任选取代的不饱和杂环; D 任选保护羧基）]}。

8. 发明授权

US06258811B1 Methods for preventing, inhibiting or treating graft rejection reactions in graft-versus-host disease (GVHD) and organ transplantation 失效
标题翻译：在移植物抗宿主病（GVHD）和器官移植中预防，抑制或治疗移植排斥反应的方法
公开(公告)号：US06258811B1
公开(公告)日：2001-07-10
申请号：US09269924
申请日：1999-04-02
申请人： Toshihiko Yamauchi , Akira Ishibashi , Naoki Tokuhara , Mitsuo Nagai
发明人： Toshihiko Yamauchi , Akira Ishibashi , Naoki Tokuhara , Mitsuo Nagai
IPC分类号： A61K3150
CPC分类号： A61K31/498 , A61K31/192 , A61K31/203 , A61K31/4025
摘要： The present invention provides remedies for graft-versus-host disease (GVHD) and graft rejection reactions in organ transplantation which comprise retinoic acid receptor (RAR) agonists as an active ingredient. Main examples thereof include 9-(4-methoxy-2,3,6-trimethylphenyl)-7,8-dimethylnona-2,4,6,8-tetraen-1-oic acid, 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)propenyl]benzoic acid, 4-{2-[5-(4,7-dimethylbenzofuran-2-yl)pyrroyl]}benzoic acid, 4-{2-[5-(5-chloro-7-ethylbenzofuran-2-yl)pyrrolyl]}benzoic acid and 4-{2-[5-(4,7-dimethylbenzothiophen-2-yl)pyrrolyl]}benzoic acid.
摘要翻译：本发明提供了包含视黄酸受体（RAR）激动剂作为活性成分的器官移植中的移植物抗宿主病（GVHD）和移植排斥反应的补救措施。其主要实例包括9-（4-甲氧基-2,3,6-三甲基苯基）-7,8-二甲基 - 2,4,6,8-四烯-1-酸，4 - [（E）-2- （5,6,7,8-四氢-5,5,8,8-四甲基萘-2-基）丙烯基]苯甲酸，4- {2- [5-（4,7-二甲基苯并呋喃-2-基）吡咯基 ]}苯甲酸，4- {2- [5-（5-氯-7-乙基苯并呋喃-2-基）吡咯基]}苯甲酸和4- {2- [5-（4,7-二甲基苯并噻吩-2-基））吡咯基]}苯甲酸。

9. 发明授权

US06355669B1 Retinoic acid agonists as preventive and therapeutic agents for nephritis 失效
标题翻译：视黄酸激动剂作为肾炎的预防和治疗剂
公开(公告)号：US06355669B1
公开(公告)日：2002-03-12
申请号：US09529675
申请日：2000-04-18
申请人： Toshihiko Yamauchi , Akira Ishibashi , Naoki Tokuhara , Mitsuo Nagai
发明人： Toshihiko Yamauchi , Akira Ishibashi , Naoki Tokuhara , Mitsuo Nagai
IPC分类号： A61K3140
CPC分类号： A61K31/695 , A61K31/00 , A61K31/40 , A61K31/4025 , A61K31/4155 , A61K31/498 , A61K31/55
摘要： The present invention provides a therapeutic or prophylactic agent as a substitute for conventional steroids or immunosuppressive agents to treat or prevent systemic erythematosus, glomerulonephritis, lupus nephritis, idiopathic thrombocytopenic purpura or autoimmune anemia. The agent comprises a retinoic acid receptor agonist, specifically a retinoic acid receptor subtype &agr; (RAR&agr;) agonist, including for example: (1) carboxylic acid compounds having condensed rings represented by the following formula: (wherein the rings L and M are condensed, are the same as or different from each other, and represent an aromatic hydrocarbon which may have a substituent group or a heterocycle which may have a substituent group; the rings A and B are independent of each other and represent an aromatic hydrocarbon ring or heterocycle which may have a substituent group; and D represents a carboxyl group which may have a protective group), (2) 4-{[(3,5-bistrimethylsilylphenyl)carbonyl]amino}benzoic acid, 4-{2-[5-(3-methoxymethyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-yl)pyrrolyl]}benzoic acid, etc.
摘要翻译：本发明提供治疗或预防药物作为常规类固醇或免疫抑制剂的替代物，用于治疗或预防全身性红斑狼疮，肾小球性肾炎，狼疮性肾炎，特发性血小板减少性紫癜或自身免疫性贫血。该试剂包括视黄酸受体激动剂，特别是视黄酸受体亚型α（RARα）激动剂，包括例如：（1）具有由下式表示的稠环的羧酸化合物：（其中环L和M缩合，表示可以具有取代基的芳香族烃或可以具有取代基的杂环，环A和B彼此独立地表示芳香族烃环或杂环，可以具有取代基; D表示可具有保护基的羧基），（2）4 - {[（3,5-双三甲基甲硅烷基苯基）羰基]氨基}苯甲酸，4- {2- [5- 3-甲氧基甲基-5,6,7,8-四氢-5,5,8,8-四甲基萘-2-基）吡咯基]}苯甲酸等

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