公开(公告)号：US20100197698A1

公开(公告)日：2010-08-05

申请号：US12665492

申请日：2008-06-19

申请人： Noriaki Gomi ,  Shinji Ina ,  Kenjirou Yamana ,  Yoshio Kaneko

发明人： Noriaki Gomi ,  Shinji Ina ,  Kenjirou Yamana ,  Yoshio Kaneko

IPC分类号： A61K31/501 ,  C07D237/14 ,  A61K31/50 ,  C07D405/12 ,  A61P7/02

CPC分类号： C07D237/14 ,  C07D401/06 ,  C07D405/12 ,  C07D417/06

摘要： To find a compound having a tissue fibrinosis-inhibitory activity and a fibrinolytic activity, and to provide a novel compound that is useful for preventing and/or treating tissue fibrinosis diseases (pulmonary fibrosis, renal fibrosis etc.), diseases caused by pathological blood clots such as ischemic heart diseases (myocardial infarction, angina), intraatrial thrombus, pulmonary embolism, deep venous thrombosis, disseminated intravascular coagulation, ischemic cerebral diseases (cerebral infarction, cerebral bleeding) and arteriosclerosis and the like. To provide a pharmaceutical drug comprising a 5-phenyl-3-pyridazinone derivative represented by the following general formula (I): and an optical isomer thereof, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, useful for preventing and/or treating disease conditions or symptoms mediated by plasminogen activator inhibitor-1.

摘要翻译： 为了找到具有组织纤维蛋白沉积抑制活性和纤维蛋白溶解活性的化合物，并提供可用于预防和/或治疗组织纤维蛋白病（肺纤维化，肾纤维化等）的新型化合物，由病理性血块引起的疾病 心肌梗塞，心绞痛，心内膜血栓，肺栓塞，深静脉血栓形成，弥散性血管内凝血，缺血性脑疾病（脑梗死，脑出血），动脉硬化等。 提供一种药物，其含有下述通式（I）表示的5-苯基-3-哒嗪酮衍生物及其旋光异构体或其药学上可接受的盐或其水合物或溶剂合物，其用于预防和/ 或治疗由纤溶酶原激活物抑制剂-1介导的疾病状况或症状。

公开(公告)号：US08106053B2

公开(公告)日：2012-01-31

申请号：US12665492

申请日：2008-06-19

申请人： Noriaki Gomi ,  Shinji Ina ,  Kenjirou Yamana ,  Yoshio Kaneko

发明人： Noriaki Gomi ,  Shinji Ina ,  Kenjirou Yamana ,  Yoshio Kaneko

IPC分类号： A61K31/50 ,  A61K31/501 ,  C07D237/02

CPC分类号： C07D237/14 ,  C07D401/06 ,  C07D405/12 ,  C07D417/06

摘要： To find a compound having a tissue fibrinosis-inhibitory activity and a fibrinolytic activity, and to provide a novel compound that is useful for preventing and/or treating tissue fibrinosis diseases (pulmonary fibrosis, renal fibrosis etc.), diseases caused by pathological blood clots such as ischemic heart diseases (myocardial infarction, angina), intraatrial thrombus, pulmonary embolism, deep venous thrombosis, disseminated intravascular coagulation, ischemic cerebral diseases (cerebral infarction, cerebral bleeding) and arteriosclerosis and the like. To provide a pharmaceutical drug comprising a 5-phenyl-3-pyridazinone derivative represented by the following general formula (I): and an optical isomer thereof, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, useful for preventing and/or treating disease conditions or symptoms mediated by plasminogen activator inhibitor-1.

摘要翻译： 为了找到具有组织纤维蛋白沉积抑制活性和纤维蛋白溶解活性的化合物，并提供可用于预防和/或治疗组织纤维蛋白病（肺纤维化，肾纤维化等）的新型化合物，由病理性血块引起的疾病 心肌梗塞，心绞痛，心内膜血栓，肺栓塞，深静脉血栓形成，弥散性血管内凝血，缺血性脑疾病（脑梗死，脑出血），动脉硬化等。 提供一种药物，其含有下述通式（I）表示的5-苯基-3-哒嗪酮衍生物及其旋光异构体或其药学上可接受的盐或其水合物或溶剂合物，其用于预防和/ 或治疗由纤溶酶原激活物抑制剂-1介导的疾病状况或症状。

公开(公告)号：US20100324091A1

公开(公告)日：2010-12-23

申请号：US12666015

申请日：2008-06-23

申请人： Noriaki Gomi ,  Shinji Ina ,  Kenjirou Yamana ,  Yoshio Kaneko

发明人： Noriaki Gomi ,  Shinji Ina ,  Kenjirou Yamana ,  Yoshio Kaneko

IPC分类号： A61K31/454 ,  C07D231/20 ,  A61K31/4152 ,  C07D401/06 ,  A61P7/02

CPC分类号： C07D231/20 ,  C07D231/22 ,  C07D401/06 ,  C07D405/12

摘要： A pyrazolone derivative represented by formula (I) below: wherein R1 to R3 are the same as defined in claims; or an optical isomer, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is provided. The novel pyrazolone derivative according to the present invention has a PAI-1 production inhibitory activity, a tissue fibrosis inhibitory activity, and a fibrolytic activity, and is effective for preventing and/or treating tissue fibrotic diseases (lung fibrosis, kidney fibrosis, etc.) and diseases of which a pathological thrombus becomes the cause, such as ischemic cardiac diseases (cardiac infarction and angina pectoris), atrial thrombus, lung embolism, deep thrombophlebitis, disseminated intravascular clotting, ischemic brain diseases (brain infarction, brain hemorrhage), and arterial sclerosis. In addition, a pharmaceutical agent for preventing and/or treating the disease conditions or the symptoms mediated by plasminogen activator inhibitor-1, comprising the novel pyrazolone derivative according to the present invention is also provided.

摘要翻译： 由下式（I）表示的吡唑啉酮衍生物：其中R1至R3与权利要求中所定义相同; 或光学异构体，其药学上可接受的盐，或其水合物或溶剂化物。 根据本发明的新型吡唑啉酮衍生物具有PAI-1产生抑制活性，组织纤维化抑制活性和纤维分解活性，对预防和/或治疗组织纤维化疾病（肺纤维化，肾纤维化等）有效 ）和病理性血栓成为原因的疾病，如缺血性心脏病（心肌梗死和心绞痛），心房血栓，肺栓塞，深部血栓性静脉炎，弥漫性血管内凝血，缺血性脑病（脑梗死，脑出血）等） 动脉硬化。 此外，还提供了包含根据本发明的新型吡唑啉酮衍生物的用于预防和/或治疗疾病状况或由纤溶酶原激活物抑制剂-1介导的症状的药剂。

公开(公告)号：US06235739B1

公开(公告)日：2001-05-22

申请号：US09202317

申请日：1998-12-11

申请人： Shinji Ina ,  Kenjirou Yamana ,  Kyoji Noda

发明人： Shinji Ina ,  Kenjirou Yamana ,  Kyoji Noda

IPC分类号： A61K3150

CPC分类号： C07D237/04

摘要： A 5-phenyl-3-pyridazinone derivative having the formula (I) wherein R1 represents an unsubstituted or substituted C1 to C8 alkyl group, C3 to C7 cycloalkyl group, or indanyl group; R2 represents a C1 to C4 alkyl group; R3 represents a hydrogen atom or an unsubstituted or substituted C1 to C5 alkyl group; a C3 to C7 cycloalkyl group; or an aryl group which may contain a heteroatom; R4 and R5 independently represent a hydrogen atom, C1 to C6 alkyl group, an unsubstituted or substituted phenyl, or a monocyclic aryl group which may contain a heteroatom; a dotted line represents a single or double bond, provided that when the dotted line represents a single bond; R6 represents a hydrogen atom or C1 to C6 alkyl group.

摘要翻译： 具有式（I）的5-苯基-3-哒嗪酮衍生物，其中R1表示未取代或取代的C1至C8烷基，C3至C7环烷基或茚满基; R2表示C1〜C4烷基; R3表示氢原子或未取代或取代的C1至C5烷基; C3至C7环烷基; 或可以含有杂原子的芳基; R4和R5独立地表示氢原子，C1-C6烷基，未取代或取代的苯基或可含有杂原子的单环芳基; 虚线表示单键或双键，条件是当虚线表示单键时; R6表示氢原子或C1〜C6烷基。

公开(公告)号：US06235736B1

公开(公告)日：2001-05-22

申请号：US09446822

申请日：2000-03-20

申请人： Shinji Ina ,  Kenjirou Yamana ,  Kyoji Noda ,  Akane Takahama ,  Toshihiko Akiyama

发明人： Shinji Ina ,  Kenjirou Yamana ,  Kyoji Noda ,  Akane Takahama ,  Toshihiko Akiyama

IPC分类号： A61K31136

CPC分类号： C07D295/116 ,  C07C225/20 ,  C07C225/22 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2601/16 ,  C07C2602/08 ,  C07C2602/42 ,  C07D211/86 ,  C07D213/38 ,  C07D215/12 ,  C07D307/20

摘要： A 3-anilino-2-cycloalkenone derivative of the formula (I): wherein, R1 represents a C1 to C8 alkyl group, which may have a substituent, except for a methyl group, a C3 to C7 cycloalkyl group, a 3-tetrahydrofuryl group, an 2-indanyl group, etc., R2 represents a C1 to C4 alkyl group, R3 represents a hydrogen atom, a C3 to C7 alkyl group, which may have a substituent, a C3 to C7 cycloalkyl group, etc., R4 represents a hydrogen atom, a C1 to C5 alkyl group, which may have a substituent, a halogen atom, etc., R5, R6, R7, and R8 independently represent a hydrogen atom, a C1 to C5 alkyl group, which may have a substituent, etc., X represents —(CR11R12)n—, wherein n is 0 to 2, R11 and R12 independently represent a hydrogen atom, a C1 to C5 alkyl group, which may have a substituent, etc. or —NR13— wherein R13 represents a hydrogen atom or a C1 to C5 alkyl group, which may have a substituent, and its optical isomers or their pharmaceutically acceptable salts or their hydrates or solvates.

摘要翻译： 式（I）的3-苯胺基-2-环烯酮酮衍生物：其中，R 1表示可以具有取代基的C1〜C8烷基，除了甲基，C3〜C7环烷基，3-四氢呋喃基 基，1,2-二氢化茚基等，R2表示C1〜C4烷基，R3表示氢原子，可具有取代基的C3〜C7烷基，C3〜C7环烷基等，R4 表示氢原子，可具有取代基的C1〜C5烷基，卤素原子等，R5，R6，R7和R8分别表示氢原子，C1〜C5烷基，可以具有 取代基等，X表示 - （CR 11 R 12）n - ，其中n为0至2，R 11和R 12独立地表示氢原子，可具有取代基的C1至C5烷基等，或-NR13-，其中 R13表示可以具有取代基的氢原子或C1〜C5烷基，及其光学异构体或其药学上可接受的盐或其水合物或溶剂化物。

公开(公告)号：US06251897B1

公开(公告)日：2001-06-26

申请号：US09230869

申请日：1999-02-01

申请人： Shinji Ina ,  Kenjirou Yamana ,  Kyoji Noda

发明人： Shinji Ina ,  Kenjirou Yamana ,  Kyoji Noda

IPC分类号： A61K31535

CPC分类号： C07D413/04 ,  C07D265/10 ,  C07D413/06 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12

摘要： A 6-phenyltetrahydro-1,3-oxazin-2-one derivative having the formula (I): wherein, R1 is an unsubstituted or substituted C1 to C8 alkyl group; an unsubstituted or substituted C3 to C7 cycloalkyl group;, etc., R2 is a C1 to C4 alkyl group, R3 is H; an unsubstituted or substituted C1 to C5 alkyl group; etc., R4 is H; an unsubstituted or substituted C1 to C6 alkyl group, and R5 and R6 are independently a hydrogen atom; an unsubstituted or substituted C1 to C5 alkyl group; etc. an optical isomer thereof, or a pharmacologically acceptable salt thereof, or a hydrate or a solvate thereof and pharmaceutical compositions containing the same, in particular a drug for the prevention or treatment of inflammatory diseases and a drug for asthma. The above 6-phenyltetrahydro-1,3-oxazin-2-one derivative has a strong type IV PDE inhibitory activity and has a bronchiodilator and antiinflammatory effects.

摘要翻译： 具有式（I）的6-苯基四氢-1,3-恶嗪-2-酮衍生物：其中，R1是未取代或取代的C1至C8烷基; 未取代或取代的C 3〜C 7环烷基等; R 2为C 1〜C 4烷基，R 3为H; 未取代或取代的C1至C5烷基; 等等，R4是H; 未取代或取代的C1至C6烷基，R5和R6独立地为氢原子; 未取代或取代的C1至C5烷基; 其光学异构体或其药理学上可接受的盐，或其水合物或溶剂化物以及含有它们的药物组合物，特别是用于预防或治疗炎性疾病的药物和用于哮喘的药物。 苯基四氢-1,3-恶嗪-2-酮衍生物具有强IV型PDE抑制活性，具有支气管扩张剂和抗炎作用。

公开(公告)号：US06265402B1

公开(公告)日：2001-07-24

申请号：US09242818

申请日：1999-02-25

申请人： Shinji Ina ,  Kenjirou Yamana ,  Kyoji Noda

发明人： Shinji Ina ,  Kenjirou Yamana ,  Kyoji Noda

IPC分类号： A61K315375

CPC分类号： C07D413/06 ,  C07D265/32

摘要： A 2-phenylmorpholin-5-one derivative having the formula (I): wherein R1 represents a C1 to C8 alkyl group, a C3 to C7 cycloalkyl group or an indanyl group, R2 represents a C1 to C4 alkyl group, R3 represents a hydrogen atom, a C1 to C5 alkyl group, etc., R4 represents a hydrogen atom, a C1 to C6 alkyl group, etc., R5, R6 represent a hydrogen atom, a C1 to C5 alkyl group, etc., an optical isomer thereof or a pharmacologically acceptable salt thereof, or a hydrate or solvate thereof and a pharmaceutical composition containing the same. The above compound has a strong type IV phosphodiesterase (PDE) inhibitory activity and has bronchodilater and antiinflammatory effects.

摘要翻译： 具有式（I）的2-苯基吗啉-5-酮衍生物：其中R1表示C1至C8烷基，C3至C7环烷基或茚满基，R2表示C1至C4烷基，R3表示氢 原子，C1〜C5烷基等，R4表示氢原子，C1〜C6烷基等，R5，R6表示氢原子，C1〜C5烷基等，其旋光异构体 或其药理学上可接受的盐，或其水合物或溶剂化物以及含有它们的药物组合物。上述化合物具有强IV型磷酸二酯酶（PDE）抑制活性并具有支气管扩张剂和抗炎作用。