公开(公告)号：US07345180B2

公开(公告)日：2008-03-18

申请号：US10541108

申请日：2004-01-30

申请人： Takuji Kakigami ,  Mitsuru Oka ,  Noriyasu Katoh ,  Masahiro Yoshida ,  Masahiro Shirai ,  Toru Murase ,  Masao Sakairi ,  Takayo Murase ,  Mitsuaki Takeuchi ,  Yuji Hayashi ,  Motohiro Takeda ,  Mitsuhiro Makino

发明人： Takuji Kakigami ,  Mitsuru Oka ,  Noriyasu Katoh ,  Masahiro Yoshida ,  Masahiro Shirai ,  Toru Murase ,  Masao Sakairi ,  Takayo Murase ,  Mitsuaki Takeuchi ,  Yuji Hayashi ,  Motohiro Takeda ,  Mitsuhiro Makino

IPC分类号： C07D487/04 ,  C07D277/06 ,  C07D209/04

CPC分类号： C07D487/04 ,  C07D207/16 ,  C07D209/42 ,  C07D209/44 ,  C07D215/54 ,  C07D217/26 ,  C07D277/62 ,  C07D311/16 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D473/34 ,  C07D513/04

摘要： A dipeptidyl peptidase IV inhibitor which is satisfactory in respect of activity, stability and safety and has an excellent action as a pharmaceutical agent. A compound represented by the following general formula or a pharmaceutically acceptable salt thereof: wherein R1 and R2 each represents hydrogen, an optionally substituted C1-6 alkyl group, or —COOR5 whereupon R5 represents hydrogen or an optionally substituted C1-6 alkyl group, or R1, R2, and a carbon atom together represent a 3- to 6-membered cycloalkyl group, R3 represents hydrogen or an optionally substituted C6-10 aryl group, R4represents a hydrogen or a cyano group, D represents —CONR6-, —CO— or —NR6CO—, R6 represents hydrogen or an optionally substituted C1-6 alkyl group, E represents —(CH2)m— whereupon m is 1 to 3, —CH2OCH2—, or —SCH2—, n is 0 to 3, and A represents an optionally substituted bicyclic heterocyclic group or bicyclic hydrocarbon group.

摘要翻译： 二肽基肽酶IV抑制剂在活性，稳定性和安全性方面令人满意，并且作为药剂具有优异的作用。 由以下通式表示的化合物或其药学上可接受的盐：其中R 1和R 2各自表示氢，任选取代的C 1-6烷基或 - COOR 5其中R 5表示氢或任选取代的C 1-6烷基，或R 1，R 2，O， >，并且碳原子一起表示3至6元环烷基，R 3表示氢或任选取代的C 6-10芳基，R 4表示 氢或氰基，D表示-CONR 6 - ， - CO-或-NR 6 CO-，R 6表示氢或 任选取代的C 1-6烷基，E表示 - （CH 2 CH 2）m - ，其中m为1至3，-CH 2 OCH 2， 或-SCH 2 - ，n为0至3，A表示任选取代的双环杂环基或双环烃基。

公开(公告)号：US20060229286A1

公开(公告)日：2006-10-12

申请号：US10541108

申请日：2004-01-30

申请人： Takuji Kakigami ,  Mitsuru Oka ,  Noriyasu Katoh ,  Masahiro Yoshida ,  Masahiro Shirai ,  Toru Murase ,  Masao Sakairi ,  Takayo Murase ,  Mitsuaki Takeuchi ,  Yuji Hayashi ,  Motohiro Takeda ,  Mitsuhiro Makino

发明人： Takuji Kakigami ,  Mitsuru Oka ,  Noriyasu Katoh ,  Masahiro Yoshida ,  Masahiro Shirai ,  Toru Murase ,  Masao Sakairi ,  Takayo Murase ,  Mitsuaki Takeuchi ,  Yuji Hayashi ,  Motohiro Takeda ,  Mitsuhiro Makino

IPC分类号： A61K31/537 ,  A61K31/445 ,  A61K31/426 ,  A61K31/401

CPC分类号： C07D487/04 ,  C07D207/16 ,  C07D209/42 ,  C07D209/44 ,  C07D215/54 ,  C07D217/26 ,  C07D277/62 ,  C07D311/16 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D473/34 ,  C07D513/04

摘要： A dipeptidyl peptidase IV inhibitor which is satisfactory in respect of activity, stability and safety and has an excellent action as a pharmaceutical agent. A compound represented by the following general formula or a pharmaceutically acceptable salt thereof: wherein R1 and R2 each represents hydrogen, an optionally substituted C1-6 alkyl group, or —COOR5 whereupon R5 represents hydrogen or an optionally substituted C1-6 alkyl group, or R1, R2, and a carbon atom together represent a 3- to 6-membered cycloalkyl group, R3 represents hydrogen or an optionally substituted C6-10 aryl group, R4 represents a hydrogen or a cyano group, D represents —CONR6—, —CO— or —NR6CO—, R6 represents hydrogen or an optionally substituted C1-6 alkyl group, E represents —(CH2)m— whereupon m is 1 to 3, —CH2OCH2—, or —SCH2—, n is 0 to 3, and A represents an optionally substituted bicyclic heterocyclic group or bicyclic hydrocarbon group.

摘要翻译： 二肽基肽酶IV抑制剂在活性，稳定性和安全性方面令人满意，并且作为药剂具有优异的作用。 由以下通式表示的化合物或其药学上可接受的盐：其中R 1和R 2各自表示氢，任选取代的C 1-6烷基或 - COOR 5其中R 5表示氢或任选取代的C 1-6烷基，或R 1，R 2，O， >，并且碳原子一起表示3至6元环烷基，R 3表示氢或任选取代的C 6-10芳基，R 4表示 氢或氰基，D表示-CONR 6 - ， - CO-或-NR 6 CO-，R 6表示氢或 任选取代的C 1-6烷基，E表示 - （CH 2 CH 2）m - ，其中m为1至3，-CH 2 OCH 2， 或-SCH 2 - ，n为0至3，A表示任选取代的双环杂环基或双环烃基。

公开(公告)号：US06809113B2

公开(公告)日：2004-10-26

申请号：US10087208

申请日：2002-02-27

申请人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

发明人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

IPC分类号： A61K3135

CPC分类号： C07D401/12 ,  C07D215/48 ,  C07D241/42 ,  C07D265/36 ,  C07D319/18 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D417/12

摘要： Compounds which are antagonists of MCP-1 function and are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection; pharmaceutical compositions comprising these compounds; and the use of these compounds and compositions in the prevention or treatment of such diseases.

摘要翻译： 作为MCP-1拮抗剂的化合物起作用，可用于预防或治疗慢性或急性炎性或自身免疫性疾病，特别是与异常淋巴细胞或单核细胞积累相关的疾病如关节炎，哮喘，动脉粥样硬化，糖尿病性肾病，炎性肠病， 克罗恩病，多发性硬化，肾炎，胰腺炎，肺纤维化，牛皮癣，再狭窄和移植排斥反应; 包含这些化合物的药物组合物; 以及这些化合物和组合物在预防或治疗这些疾病中的用途。

公开(公告)号：US07081473B2

公开(公告)日：2006-07-25

申请号：US10514027

申请日：2003-05-20

申请人： Yoshiharu Tsubamoto ,  Akira Tashita ,  Yukari Kobara ,  Takuji Kakigami

发明人： Yoshiharu Tsubamoto ,  Akira Tashita ,  Yukari Kobara ,  Takuji Kakigami

IPC分类号： A61K31/166 ,  A61K31/4045 ,  A61P3/04 ,  C07C243/18 ,  C07D209/08 ,  C07D409/06

CPC分类号： C07C243/38 ,  A61K31/166 ,  A61K31/4045 ,  C07D209/08 ,  C07D209/14 ,  C07D409/06

摘要： The present invention provides a low-molecular inhibitor of GIP functions and, further, an agent for preventing/ameliorating obesity based on inhibition of GIP functions, which comprises, as an active ingredient, a compound represented by the following general formula (I): (wherein R1 represents hydrogen, halogen, a nitro group or a cyano group, R2 and R3 each represent hydrogen or halogen, hydrogen or a methoxy group, or both R2 and R3 may form an optionally substituted benzene or pyrrole ring, and A represents nitrogen or C—R4 whereupon R4 represents hydrogen, an optionally substituted C1 to C6 alkyl group, —OR7, —NR8R9, —NHCO—R10 or —SO2—R11 or may, together with R3, form an optionally substituted benzene or pyrrole ring, R7, R8 and R9 each represent hydrogen or an optionally substituted C1 to C6 alkyl group, R10 represents a C1 to C6 alkyl group or the like, and R1 represents an optionally substituted morpholyl group or the like) or a pharmaceutically acceptable salt thereof.

摘要翻译： 本发明提供了GIP功能的低分子抑制剂，另外，作为活性成分，由以下通式（I）表示的化合物作为活性成分，可以抑制GIP功能的抑制/改善， （其中R 1表示氢，卤素，硝基或氰基，R 2和R 3各自表示氢或卤素，氢， 或甲氧基，或者R 2和R 3都可以形成任选取代的苯或吡咯环，A表示氮或CR 4， 其中R 4表示氢，任选取代的C 1 -C 6烷基，-OR 7，-NR 8 R 9， 或者可以与R 3，R 3，R 3，R 11， 形成任选取代的苯或吡咯环，R 7，R 8和R 9各自表示氢或任选取代的C 1至C 6 Al 烷基，R 10表示C1〜C6烷基等，R 1表示任选取代的吗啉基等）或其药学上可接受的盐。

公开(公告)号：US5539125A

公开(公告)日：1996-07-23

申请号：US489709

申请日：1995-06-13

申请人： Yutaka Baba ,  Toshinao Usui ,  Takuji Kakigami ,  Yoshiro Ozeki ,  Katsura Tsukamoto ,  Nobuyuki Itoh

发明人： Yutaka Baba ,  Toshinao Usui ,  Takuji Kakigami ,  Yoshiro Ozeki ,  Katsura Tsukamoto ,  Nobuyuki Itoh

IPC分类号： A61K31/40 ,  A61P1/00 ,  C07D487/04 ,  C07D403/12 ,  C07D405/12

CPC分类号： C07D487/04

摘要： There are disclosed a 1-azabicyclo[3.3.0]octan derivative of the formula ##STR1## wherein n is an integer of 1-5; and Ar is an aromatic residue. a pharmacologically acceptable salt of the compound, a process for the preparation of the compound and salt as well as use thereof as hypermotility agents.

摘要翻译： 公开了式（I）的1-氮杂双环[3.3.0]辛烷衍生物，其中n是1-5的整数; 并且Ar是芳族残基。 化合物的药理学上可接受的盐，化合物和盐的制备方法以及其作为超运动剂的用途。

公开(公告)号：US5442077A

公开(公告)日：1995-08-15

申请号：US285719

申请日：1994-08-04

申请人： Yutaka Baba ,  Toshinao Usui ,  Noriyuki Iwata ,  Takuji Kakigami ,  Yoshiro Ozeki ,  Katsura Tsukamoto ,  Nobuyuki Ito

发明人： Yutaka Baba ,  Toshinao Usui ,  Noriyuki Iwata ,  Takuji Kakigami ,  Yoshiro Ozeki ,  Katsura Tsukamoto ,  Nobuyuki Ito

IPC分类号： A61K31/40 ,  A61P1/00 ,  C07D487/04

CPC分类号： C07D487/04

摘要： There are disclosed a benzo[b]furancarboxamide derivative of the formula ##STR1## wherein R.sup.a, R.sup.b, R.sup.c and R.sup.d are a hydrogen atom or lower alkyl group, respectively; R.sup.e is a hydrogen atom, amino radical, lower alkylamino group or acylamino group; X is a hydrogen atom or halogen atom; and n is an integer of 1-5,and including racemic compounds and stereo-isomers thereof, a salt of the compounds, a process for the preparation of the compounds and salts as well as use thereof for improving hypermotility.

摘要翻译： 公开了式（I）的苯并[b]呋喃甲酰胺衍生物，其中R a，R b，R c和R d分别是氢原子或低级烷基; Re为氢原子，氨基，低级烷基氨基或酰氨基; X是氢原子或卤素原子; n为1-5的整数，并且包括外消旋化合物及其立体异构体，化合物的盐，化合物和盐的制备方法以及其用于改善过度运动性的用途。

公开(公告)号：US5171865A

公开(公告)日：1992-12-15

申请号：US664686

申请日：1991-03-05

申请人： Masayasu Kurono ,  Yasuaki Kondo ,  Kenji Miura ,  Toshinao Usui ,  Ryoichi Unno ,  Takuji Kakigami ,  Kiichi Sawai

发明人： Masayasu Kurono ,  Yasuaki Kondo ,  Kenji Miura ,  Toshinao Usui ,  Ryoichi Unno ,  Takuji Kakigami ,  Kiichi Sawai

IPC分类号： C07C59/68 ,  C07D311/24

CPC分类号： C07D311/24 ,  C07C59/68

摘要： A process for the preparation of optically active 4-oxo-1-benzopyran-2-carboxylic acid derivatives of the formula ##STR1## wherein X and Y are hydrogen atom, halogen atom or alkyl group, and R.sub.1 is hydrogen atom or alkyl group,intermediates thereof, as well as a process for the preparation of the intermediates.

摘要翻译： 制备下式的光学活性4-氧代-1-苯并吡喃-2-羧酸衍生物的方法，其中X和Y是氢原子，卤素原子或烷基，R 1是氢原子或烷基， 其中间体，以及制备中间体的方法。

公开(公告)号：US06998407B2

公开(公告)日：2006-02-14

申请号：US10716652

申请日：2003-11-18

申请人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

发明人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

IPC分类号： A61K31/36 ,  A61K31/343 ,  C07D307/79 ,  C07D317/60

CPC分类号： C07D235/06 ,  C07D209/08 ,  C07D249/18 ,  C07D263/56 ,  C07D307/79 ,  C07D317/68 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D417/12

摘要： Chemical compounds which are antagonists of Monocyte Chemoattractant Protein-1 (MCP-1) function, pharmaceutical compositions comprising these compounds, methods of treatment employing these compounds and compositions, and processes for preparing these compounds. The compounds are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection.

摘要翻译： 作为单核细胞趋化蛋白-1（MCP-1）功能拮抗剂的化合物，包含这些化合物的药物组合物，使用这些化合物和组合物的治疗方法，以及制备这些化合物的方法。 该化合物可用于预防或治疗慢性或急性炎性或自身免疫疾病，特别是与异常淋巴细胞或单核细胞积累相关的疾病，如关节炎，哮喘，动脉粥样硬化，糖尿病性肾病，炎性肠病，克罗恩病，多发性硬化，肾炎， 胰腺炎，肺纤维化，牛皮癣，再狭窄和移植排斥。

公开(公告)号：US06992086B2

公开(公告)日：2006-01-31

申请号：US10716363

申请日：2003-11-17

申请人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

发明人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

IPC分类号： A61K31/496 ,  A61K31/437 ,  C07D498/04 ,  C07D471/04 ,  A61P37/00

CPC分类号： C07D471/04 ,  A61K31/437 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/5513 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention relates to chemical compounds, pharmaceutical compositions comprising said compounds, uses of said compounds and compositions, methods of treatment employing said compounds and compositions, and processes for preparing said compounds. Specifically, this invention relates to novel compounds which are antagonists of MCP-1 function and are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection. More specifically, the invention is related to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases.

公开(公告)号：US06677365B2

公开(公告)日：2004-01-13

申请号：US10106881

申请日：2002-03-25

申请人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

发明人： Edgardo Laborde ,  Louise Robinson ,  Fanying Meng ,  Brian T. Peterson ,  Hugo O. Villar ,  Steven E. Anuskiewicz ,  Yoshiro Ishiwata ,  Shoji Yokochi ,  Yukiharu Matsumoto ,  Takuji Kakigami ,  Hideaki Inagaki ,  Takahito Jomori ,  Kouji Matsushima

IPC分类号： A61K3142

CPC分类号： C07D235/06 ,  C07D209/08 ,  C07D249/18 ,  C07D263/56 ,  C07D307/79 ,  C07D317/68 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D417/12

摘要： Chemical compounds which are antagonists of Monocyte Chemoattractant Protein-1 (MCP-1) function, pharmaceutical compositions comprising these compounds, methods of treatment employing these compounds and compositions, and processes for preparing these compounds. The compounds are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection.