公开(公告)号：US07951825B2

公开(公告)日：2011-05-31

申请号：US12696327

申请日：2010-01-29

申请人： Hironori Harada ,  Kazuyuki Hattori ,  Kazuya Fujita ,  Masataka Morita ,  Sunao Imada ,  Yoshito Abe ,  Hiromichi Itani ,  Tatsuaki Morokata ,  Hideo Tsutsumi

发明人： Hironori Harada ,  Kazuyuki Hattori ,  Kazuya Fujita ,  Masataka Morita ,  Sunao Imada ,  Yoshito Abe ,  Hiromichi Itani ,  Tatsuaki Morokata ,  Hideo Tsutsumi

IPC分类号： C07D413/02 ,  C07D413/14 ,  C07D401/02 ,  C07D401/14 ,  A61K31/443

CPC分类号： C07D413/04 ,  C07D417/04 ,  C07D471/04

摘要： To provide a useful compound as an active ingredient for a preventing and/or treating agent for rejection in the transplantation of an organ, bone marrow, or a tissue, an autoimmune disease, or the like, which has an excellent S1P1 agonist activity.Since the compound of the invention has an S1P1 agonist activity, it is useful as an active ingredient for a treating or preventing agent for a disease caused by unfavorable lymphocytic infiltration, for example, an autoimmune disease such as graft rejection in the transplantation of an organ, bone marrow, or a tissue, a graft-versus-host disease, rheumatic arthritis, multiple sclerosis, systemic lupus erythematosus, a nephrotic syndrome, encephalomeningitis, myasthenia gravis, pancreatitis, hepatitis, nephritis, diabetes, pulmonary disorder, asthma, atopic dermatitis, inflammatory bowel disease, atherosclerosis, ischemia-reperfusion injury, or an inflammatory disease, and further, a disease caused by the abnormal growth or accumulation of cells such as cancer and leukemia.

摘要翻译： 为了提供具有优异的S1P1激动剂活性的器官，骨髓或组织，自身免疫疾病等的移植中的预防和/或治疗剂的有效成分的有用化合物。 由于本发明的化合物具有S1P1激动剂活性，因此可用作治疗或预防由不利淋巴细胞浸润引起的疾病的活性成分，例如自体免疫疾病例如器官移植中的移植排斥反应 骨髓或组织，移植物抗宿主病，风湿性关节炎，多发性硬化症，系统性红斑狼疮，肾病综合征，脑炎，重症肌无力，胰腺炎，肝炎，肾炎，糖尿病，肺病，哮喘，特应性皮炎 炎症性肠病，动脉粥样硬化，缺血再灌注损伤或炎性疾病，以及由细胞如癌症和白血病的异常生长或积累引起的疾病。

公开(公告)号：US07750155B2

公开(公告)日：2010-07-06

申请号：US12278580

申请日：2007-02-06

申请人： Fumiyuki Shirai ,  Hideo Tsutsumi ,  Hiromichi Itani ,  Yoshihiro Kozuki ,  Yoshiteru Eikyu ,  Taro Masunaga

发明人： Fumiyuki Shirai ,  Hideo Tsutsumi ,  Hiromichi Itani ,  Yoshihiro Kozuki ,  Yoshiteru Eikyu ,  Taro Masunaga

IPC分类号： C07D241/02

CPC分类号： C07D409/14 ,  C07D401/12 ,  C07D403/12

摘要： This invention relates to novel N-hydroxyacrylamide compounds of formula (I) and pharmaceutically acceptable salts thereof. More particularly, it relates to novel N-hydroxyacrylamide compounds and pharmaceutically acceptable salts thereof which act as a HDAC inhibitor, to a pharmaceutical composition comprising the same and to a method of using the same therapeutically in the treatment and/or prevention of HDAC-related disease.

摘要翻译： 本发明涉及式（I）的新型N-羟基丙烯酰胺化合物及其药学上可接受的盐。 更具体地说，本发明涉及作为HDAC抑制剂的新型N-羟基丙烯酰胺化合物及其药学上可接受的盐，涉及含有该N-羟基丙烯酰胺的HDAC抑制剂的药物组合物及其在治疗和/或预防HDAC相关性中的用途 疾病。

公开(公告)号：US07678820B2

公开(公告)日：2010-03-16

申请号：US12244102

申请日：2008-10-02

申请人： Hironori Harada ,  Kazuyuki Hattori ,  Kazuya Fujita ,  Masataka Morita ,  Sunao Imada ,  Yoshito Abe ,  Hiromichi Itani ,  Tatsuaki Morokata ,  Hideo Tsutsumi

发明人： Hironori Harada ,  Kazuyuki Hattori ,  Kazuya Fujita ,  Masataka Morita ,  Sunao Imada ,  Yoshito Abe ,  Hiromichi Itani ,  Tatsuaki Morokata ,  Hideo Tsutsumi

IPC分类号： A61K31/4245 ,  C07D271/06

CPC分类号： C07D413/04 ,  C07D417/04 ,  C07D471/04

摘要： To provide a useful compound as an active ingredient for a preventing and/or treating agent for rejection in the transplantation of an organ, bone marrow, or a tissue, an autoimmune disease, or the like, which has an excellent S1P1 agonist activity. Since the compound of the invention has an S1P1 agonist activity, it is useful as an active ingredient for a treating or preventing agent for a disease caused by unfavorable lymphocytic infiltration, for example, an autoimmune disease such as graft rejection in the transplantation of an organ, bone marrow, or a tissue, a graft-versus-host disease, rheumatic arthritis, multiple sclerosis, systemic lupus erythematosus, a nephrotic syndrome, encephalomeningitis, myasthenia gravis, pancreatitis, hepatitis, nephritis, diabetes, pulmonary disorder, asthma, atopic dermatitis, inflammatory bowel disease, atherosclerosis, ischemia-reperfusion injury, or an inflammatory disease, and further, a disease caused by the abnormal growth or accumulation of cells such as cancer and leukemia.

摘要翻译： 为了提供具有优异的S1P1激动剂活性的器官，骨髓或组织，自身免疫疾病等的移植中的预防和/或治疗剂的有效成分的有用化合物。 由于本发明的化合物具有S1P1激动剂活性，因此可用作治疗或预防由不利淋巴细胞浸润引起的疾病的活性成分，例如自体免疫疾病例如器官移植中的移植排斥反应 骨髓或组织，移植物抗宿主病，风湿性关节炎，多发性硬化症，系统性红斑狼疮，肾病综合征，脑炎，重症肌无力，胰腺炎，肝炎，肾炎，糖尿病，肺病，哮喘，特应性皮炎 炎症性肠病，动脉粥样硬化，缺血再灌注损伤或炎性疾病，以及由细胞如癌症和白血病的异常生长或积累引起的疾病。

公开(公告)号：US20090054465A1

公开(公告)日：2009-02-26

申请号：US12278580

申请日：2007-02-06

申请人： Fumiyuki Shirai ,  Hideo Tsutsumi ,  Hiromichi Itani ,  Yoshihiro Kozuki ,  Yoshiteru Eikyu ,  Taro Masunaga

发明人： Fumiyuki Shirai ,  Hideo Tsutsumi ,  Hiromichi Itani ,  Yoshihiro Kozuki ,  Yoshiteru Eikyu ,  Taro Masunaga

IPC分类号： A61K31/497 ,  C07D403/12 ,  C07D401/12 ,  A61P29/00 ,  A61P3/00 ,  A61P37/00

CPC分类号： C07D409/14 ,  C07D401/12 ,  C07D403/12

摘要： This invention relates to novel N-hydroxyacrylamide compounds of formula (I) and pharmaceutically acceptable salts thereof. More particularly, it relates to novel N-hydroxyacrylamide compounds and pharmaceutically acceptable salts thereof which act as a HDAC inhibitor, to a pharmaceutical composition comprising the same and to a method of using the same therapeutically in the treatment and/or prevention of HDAC-related disease.

摘要翻译： 本发明涉及式（I）的新型N-羟基丙烯酰胺化合物及其药学上可接受的盐。 更具体地说，本发明涉及作为HDAC抑制剂的新型N-羟基丙烯酰胺化合物及其药学上可接受的盐，涉及含有该N-羟基丙烯酰胺的HDAC抑制剂的药物组合物及其在治疗和/或预防HDAC相关性中的用途 疾病。

公开(公告)号：US6124456A

公开(公告)日：2000-09-26

申请号：US147543

申请日：1999-01-19

申请人： Atsushi Akahane ,  Satoru Kuroda ,  Hiromichi Itani ,  Yasuyo Shimizu

发明人： Atsushi Akahane ,  Satoru Kuroda ,  Hiromichi Itani ,  Yasuyo Shimizu

IPC分类号： A61K31/501 ,  A61P1/04 ,  A61P3/10 ,  A61P9/00 ,  A61P11/06 ,  A61P13/12 ,  A61P25/00 ,  A61P37/06 ,  A61P43/00 ,  C07D471/04 ,  A61K31/497

CPC分类号： C07D471/04

摘要： A pyrazolopyridine compound of formula (I) wherein R.sup.1 is aryl, and R.sup.2 is lower alkyl substituted with unsaturated 3 to 8-membered heteromonocyclic group containing 1 or 2 sulfur atom(s) and 1 to 3 nitrogen atom(s) which may have one or more substituent(s); a group of formula (1) wherein R.sup.3 is hydrogen, lower alkyl, ar(lower)alkyl or acyl, R.sup.4 is hydrogen or hydroxy, A is lower alkylene, m is an integer of 0 or 1, and n is an integer of 1 or 2; a group of formula (2) wherein R.sup.5 and R.sup.6 are each lower alkyl; or quinuclidinyl, or a salt the The pyrazolopyridine compound (I) and a salt thereof of the present invention are adenosine antagonists and are useful for the prevention and/or treatment of depression, dementia (e.g. Alzheimer's disease, cerebrovascular dementia, Parkinson's disease, etc.), anxiety, pain, cerebrovascular disease (e.g. stroke, etc.), heart failure, and the like.

摘要翻译： PCT No.PCT / JP97 / 02493 Sec。 371日期1999年1月19日 102（e）1999年1月19日PCT PCT 1997年7月17日PCT公布。 第WO98 / 03507号公报 日本1998年1月29日，式（I）的吡唑并吡啶化合物，其中R1为芳基，R2为被1或2个硫原子和1〜3个氮原子（s）的不饱和3〜8元杂单环取代的低级烷基 ），其可以具有一个或多个取代基; 式（1）的基团，其中R 3是氢，低级烷基，芳基（低级）烷基或酰基，R 4是氢或羟基，A是低级亚烷基，m是0或1的整数，n是整数1 或2; 式（2）的基团，其中R 5和R 6各自为低级烷基; 或奎宁环基或其盐本发明的吡唑并吡啶化合物（I）及其盐是腺苷拮抗剂，可用于预防和/或治疗抑郁症，痴呆（例如阿尔茨海默病，脑血管性痴呆，帕金森病等） ），焦虑，疼痛，脑血管疾病（例如中风等），心力衰竭等。

公开(公告)号：US20090076070A1

公开(公告)日：2009-03-19

申请号：US12244102

申请日：2008-10-02

申请人： Hironori HARADA ,  Kazuyuki Hattori ,  Kazuya Fujita ,  Masataka Morita ,  Sunao Imada ,  Yoshito Abe ,  Hiromichi Itani ,  Tatsuaki Morokata ,  Hideo Tsutsumi

发明人： Hironori HARADA ,  Kazuyuki Hattori ,  Kazuya Fujita ,  Masataka Morita ,  Sunao Imada ,  Yoshito Abe ,  Hiromichi Itani ,  Tatsuaki Morokata ,  Hideo Tsutsumi

IPC分类号： A61K31/4245 ,  C07D413/14 ,  A61K31/437 ,  A61P35/02 ,  A61P19/02 ,  A61P1/00 ,  A61P9/10 ,  A61P37/06 ,  A61P35/00 ,  A61K31/4709

CPC分类号： C07D413/04 ,  C07D417/04 ,  C07D471/04

摘要： [Problems] To provide a useful compound as an active ingredient for a preventing and/or treating agent for rejection in the transplantation of an organ, bone marrow, or a tissue, an autoimmune disease, or the like, which has an excellent S1P1 agonist activity.[Means for Solving] Since the compound of the invention has an S1P1 agonist activity, it is useful as an active ingredient for a treating or preventing agent for a disease caused by unfavorable lymphocytic infiltration, for example, an autoimmune disease such as graft rejection in the transplantation of an organ, bone marrow, or a tissue, a graft-versus-host disease, rheumatic arthritis, multiple sclerosis, systemic lupus erythematosus, a nephrotic syndrome, encephalomeningitis, myasthenia gravis, pancreatitis, hepatitis, nephritis, diabetes, pulmonary disorder, asthma, atopic dermatitis, inflammatory bowel disease, atherosclerosis, ischemia-reperfusion injury, or an inflammatory disease, and further, a disease caused by the abnormal growth or accumulation of cells such as cancer and leukemia.

摘要翻译： [问题]提供一种有用的化合物作为活性成分，用于预防和/或治疗移植器官，骨髓或组织，自身免疫疾病等中的排斥反应，其具有优异的S1P1激动剂 活动。 [解决手段]由于本发明的化合物具有S1P1激动剂活性，因此可用作由不利的淋巴细胞浸润引起的疾病的治疗或预防剂的活性成分，例如自身免疫性疾病例如移植排斥反应 器官移植，骨髓或组织，移植物抗宿主病，风湿性关节炎，多发性硬化，系统性红斑狼疮，肾病综合征，脑炎，重症肌无力，胰腺炎，肝炎，肾炎，糖尿病，肺功能障碍 哮喘，特应性皮炎，炎症性肠病，动脉粥样硬化，局部缺血再灌注损伤，炎症性疾病等疾病，以及癌症，白血病等细胞异常生长或积累引起的疾病。

公开(公告)号：US06355640B1

公开(公告)日：2002-03-12

申请号：US09072696

申请日：1998-05-06

申请人： Atsushi Akahane ,  Shintaro Nishimura ,  Hiromichi Itani ,  Kieran P. M. Durkin

发明人： Atsushi Akahane ,  Shintaro Nishimura ,  Hiromichi Itani ,  Kieran P. M. Durkin

IPC分类号： A61K31495

CPC分类号： C07D471/04

摘要： The present invention relates to a novel pyrazolopyridine compound of the following formula: wherein R1 is aryl, and R2 is cyclo(lower)alkyl which may have one or more suitable substituent(s), etc; and a pharmaceutically acceptable salt thereof, which is useful as a medicament; the processes for the preparation of said pyrazolopyridine compound or a salt thereof; a pharmaceutical composition comprising said pyrazolopyridine compound or a pharmaceutically acceptable salt thereof; etc.

摘要翻译： 本发明涉及下式的新型吡唑并吡啶化合物：其中R1为芳基，R2为可具有一个或多个合适取代基的环（低级）烷基等;及其药学上可接受的盐，其可用作 药物; 所述吡唑并吡啶化合物或其盐的制备方法; 包含所述吡唑并吡啶化合物或其药学上可接受的盐的药物组合物; 等等

公开(公告)号：US4831041A

公开(公告)日：1989-05-16

申请号：US119577

申请日：1987-11-12

申请人： Youichi Shiokawa ,  Masanobu Nagano ,  Hiromichi Itani

发明人： Youichi Shiokawa ,  Masanobu Nagano ,  Hiromichi Itani

IPC分类号： C07D213/73 ,  C07D471/04

CPC分类号： C07D213/73 ,  C07D471/04

摘要： The invention relates to an imidazopyridine compound of the formula: ##STR1## wherein R.sup.1 is lower alkynyl, lower alkynyloxy(lower)alkyl or N,N-di(lower)alkylamino(lower)alkynyl,R.sup.2 is lower alkyl,R.sup.3 is mono (or di or tri)-phenyl(lower)alkyl substituted by one or more substituent(s) selected from cyano, carbamoyl, mono (or di or tri(phenyl(lower)alkylamino, acylamino, carboxy, esterified carboxy, hydroxy, hydroxy(lower)alkyl, acyloxy(lower)alkyl, acyloxy, mono (or di or tri)phenyl(lower)alkoxy, lower alkoxy(lower)alkoxy, tetrahydropyranyloxy, and acylamino(lower)alkyl or mono (or di or tri) phenyl(lower)alkyl substituted by lower alkyl and one additional substituent selected from hydroxy(lower)alkyl, amino, N-lower alkyl-N-acylamino, mono (or di or tri)phenyl(lower)alkylamino, acylamino and lower alkylamino, andR.sup.4 is hydrogen or lower alkyl, and a pharmaceutically acceptable salt thereof, useful in the treatment of ulcers.

公开(公告)号：US4782055A

公开(公告)日：1988-11-01

申请号：US942379

申请日：1986-12-16

申请人： Ikuo Ueda ,  Youichi Shiokawa ,  Kazuhiko Take ,  Hiromichi Itani

发明人： Ikuo Ueda ,  Youichi Shiokawa ,  Kazuhiko Take ,  Hiromichi Itani

IPC分类号： C07D471/04 ,  C07D487/04 ,  A61K31/435

CPC分类号： C07D471/04 ,  C07D487/04

摘要： The present invention relates to imidazopyridine compounds of the formula: ##STR1## wherein R.sup.1 is lower alkynyl or lower alkynyloxy(lower)-alkyl,R.sup.2 is lower alkyl, andR.sup.3 is ar(lower)alkyl having lower alkoxy, lower alkylthio, nitro or lower alkanesulfonyl, ar(lower)alkyl having nitro and one or two additional substituent(s) selected from nitro and lower alkyl, or heterocyclic(lower)alkyl which may have suitable substituent(s), and to their utility.The compounds have antiulcerative properties.

摘要翻译： 本发明涉及下式的咪唑并吡啶化合物：其中R 1是低级炔基或低级炔氧基（低级） - 烷基，R 2是低级烷基，R 3是具有低级烷氧基，低级烷硫基，硝基或 低级烷基磺酰基，具有硝基的芳（低级）烷基和选自硝基和低级烷基的一个或两个另外的取代基或可具有合适取代基的杂环（低级）烷基，以及它们的用途。 该化合物具有抗溃疡性质。

公开(公告)号：US20100168159A1

公开(公告)日：2010-07-01

申请号：US12696327

申请日：2010-01-29

申请人： Hironori Harada ,  Kazuyuki Hattori ,  Kazuya Fujita ,  Masataka Morita ,  Sunao Imada ,  Yoshito Abe ,  Hiromichi Itani ,  Tatsuaki Morokata ,  Hideo Tsutsumi

发明人： Hironori Harada ,  Kazuyuki Hattori ,  Kazuya Fujita ,  Masataka Morita ,  Sunao Imada ,  Yoshito Abe ,  Hiromichi Itani ,  Tatsuaki Morokata ,  Hideo Tsutsumi

IPC分类号： A61K31/4439 ,  A61K31/4709 ,  C07D471/04 ,  C07D413/14 ,  A61P35/02 ,  A61P37/06 ,  A61P29/00 ,  A61P9/10 ,  A61P35/00

CPC分类号： C07D413/04 ,  C07D417/04 ,  C07D471/04

摘要： [Problems]To provide a useful compound as an active ingredient for a preventing and/or treating agent for rejection in the transplantation of an organ, bone marrow, or a tissue, an autoimmune disease, or the like, which has an excellent S1P1 agonist activity.[Means for solving]Since the compound of the invention has an S1P1 agonist activity, it is useful as an active ingredient for a treating or preventing agent for a disease caused by unfavorable lymphocytic infiltration, for example, an autoimmune disease such as graft rejection in the transplantation of an organ, bone marrow, or a tissue, a graft-versus-host disease, rheumatic arthritis, multiple sclerosis, systemic lupus erythematosus, a nephrotic syndrome, encephalomeningitis, myasthenia gravis, pancreatitis, hepatitis, nephritis, diabetes, pulmonary disorder, asthma, atopic dermatitis, inflammatory bowel disease, atherosclerosis, ischemia-reperfusion injury, or an inflammatory disease, and further, a disease caused by the abnormal growth or accumulation of cells such as cancer and leukemia.

摘要翻译： [问题]提供一种有用的化合物作为活性成分，用于预防和/或治疗移植器官，骨髓或组织，自身免疫疾病等中的排斥反应，其具有优异的S1P1激动剂 活动。 [解决方法]由于本发明的化合物具有S1P1激动剂活性，因此可用作由不利的淋巴细胞浸润引起的疾病的治疗或预防剂的活性成分，例如自身免疫性疾病如移植排斥反应 器官移植，骨髓或组织，移植物抗宿主病，风湿性关节炎，多发性硬化，系统性红斑狼疮，肾病综合征，脑炎，重症肌无力，胰腺炎，肝炎，肾炎，糖尿病，肺功能障碍 哮喘，特应性皮炎，炎症性肠病，动脉粥样硬化，局部缺血再灌注损伤，炎症性疾病等疾病，以及癌症，白血病等细胞异常生长或积累引起的疾病。