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公开(公告)号：US20060034832A1
公开(公告)日：2006-02-16
申请号：US10512587
申请日：2003-04-24
IPC分类号： A61K39/395 , A61K31/5415
CPC分类号： C07D417/04 , A61K31/00 , A61K31/5415 , C07D279/08 , G01N2333/52 , G01N2500/02
摘要： The cell death inhibitor comprising a substance capable of binding to macrophage migration inhibitory factor is useful as a preventive/therapeutic agent for, e.g., heart diseases, neurodegenerative diseases, cerebrovascular diseases, central nervous infections, traumatic diseases, demyelinating diseases, bone/joint diseases, kidney diseases, liver diseases, myelodysplastic diseases, arteriosclerosis, diabetes, pulmonary hypertension, sepsis, inflammatory bowel diseases, autoimmune diseases, failure accompanying rejection in organ transplantation, AIDS, cancer, etc.
摘要翻译： 包含能够结合巨噬细胞迁移抑制因子的物质的细胞死亡抑制剂可用作例如心脏病，神经变性疾病，脑血管疾病，中枢神经感染，创伤性疾病，脱髓鞘疾病，骨/关节疾病的预防/治疗剂 肾脏疾病，肝脏疾病，骨髓增生异常性疾病，动脉硬化，糖尿病，肺动脉高压，败血症，炎症性肠病，自身免疫疾病，器官移植排斥反应失败，艾滋病，癌症等。
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公开(公告)号：US20100099106A1
公开(公告)日：2010-04-22
申请号：US12576232
申请日：2009-10-08
申请人： Haruhide Kimura , Yoshimi Sato , Masayuki Takizawa
发明人： Haruhide Kimura , Yoshimi Sato , Masayuki Takizawa
IPC分类号： C12Q1/68
CPC分类号： C07D417/04 , A61K31/00 , A61K31/5415 , C07D279/08 , G01N2333/52 , G01N2500/02
摘要： The cell death inhibitor comprising a substance capable of binding to macrophage migration inhibitory factor is useful as a preventive/therapeutic agent for, e.g., heart diseases, neurodegenerative diseases, cerebrovascular diseases, central nervous infections, traumatic diseases, demyelinating diseases, bone/joint diseases, kidney diseases, liver diseases, myelodysplastic diseases, arteriosclerosis, diabetes, pulmonary hypertension, sepsis, inflammatory bowel diseases, autoimmune diseases, failure accompanying rejection in organ transplantation, AIDS, cancer, etc.
摘要翻译： 包含能够结合巨噬细胞迁移抑制因子的物质的细胞死亡抑制剂可用作例如心脏病，神经变性疾病，脑血管疾病，中枢神经感染，创伤性疾病，脱髓鞘疾病，骨/关节疾病的预防/治疗剂 肾脏疾病，肝脏疾病，骨髓增生异常性疾病，动脉硬化，糖尿病，肺动脉高压，败血症，炎症性肠病，自身免疫疾病，器官移植排斥反应失败，艾滋病，癌症等。
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公开(公告)号：US08173360B2
公开(公告)日：2012-05-08
申请号：US12576232
申请日：2009-10-08
CPC分类号： C07D417/04 , A61K31/00 , A61K31/5415 , C07D279/08 , G01N2333/52 , G01N2500/02
摘要： The cell death inhibitor comprising a substance capable of binding to macrophage migration inhibitory factor is useful as a preventive/therapeutic agent for, e.g., heart diseases, neurodegenerative diseases, cerebrovascular diseases, central nervous infections, traumatic diseases, demyelinating diseases, bone/joint diseases, kidney diseases, liver diseases, myelodysplastic diseases, arteriosclerosis, diabetes, pulmonary hypertension, sepsis, inflammatory bowel diseases, autoimmune diseases, failure accompanying rejection in organ transplantation, AIDS, cancer, etc.
摘要翻译： 包含能够结合巨噬细胞迁移抑制因子的物质的细胞死亡抑制剂可用作例如心脏病，神经变性疾病，脑血管疾病，中枢神经感染，创伤性疾病，脱髓鞘疾病，骨/关节疾病的预防/治疗剂 肾脏疾病，肝脏疾病，骨髓增生异常性疾病，动脉硬化，糖尿病，肺动脉高压，败血症，炎性肠病，自身免疫疾病，器官移植排斥反应失败，艾滋病，癌症等。
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公开(公告)号：US20100279311A1
公开(公告)日：2010-11-04
申请号：US12810585
申请日：2008-12-26
申请人： Haruhide Kimura
发明人： Haruhide Kimura
IPC分类号： G01N33/53 , C12Q1/02 , C07D513/04
CPC分类号： G01N33/6872 , G01N2500/04 , G01N2500/10
摘要： The invention provides a screening method and screening kit for a cell protecting agent. Specifically, the invention provides a method for screening a cell protecting agent showing an Hsp90-binding activity and a heat shock protein expression-inducing activity but having no Hsp90 client protein degradation-promoting activity. The method comprises the following steps (1) to (3): (1) measuring the binding property of a test compound to Hsp90; (2) measuring the activity of a test compound to induce the expression of a heat shock protein, or measuring the activity of a test compound to disrupt an Hsp90/HSF-1 complex, by using a cell capable of expressing the heat shock protein; and (3) measuring the activity of a test compound to induce the degradation of an Hsp90 client protein by using a cell capable of expressing the Hsp90 client protein. The invention further provides specifically a kit for screening a cell protecting agent, comprising (1) Hsp90; (2) a reagent for measuring the heat shock protein expression-inducing activity; (3) an imidazothiazine derivative; and (4) a reagent for quantifying an Hsp90 client protein.
摘要翻译： 本发明提供了一种细胞保护剂的筛选方法和筛选试剂盒。 具体地说，本发明提供一种筛选显示Hsp90结合活性和热休克蛋白表达诱导活性但不具有Hsp90客户蛋白降解促进活性的细胞保护剂的方法。 该方法包括以下步骤（1）至（3）：（1）测试化合物与Hsp90的结合性; （2）通过使用能够表达热休克蛋白的细胞，测量受试化合物的活性以诱导热休克蛋白的表达，或测量测试化合物破坏Hsp90 / HSF-1复合物的活性; 和（3）通过使用能够表达Hsp90客户端蛋白质的细胞来测量受试化合物的活性以诱导Hsp90客户蛋白质的降解。 本发明还特别提供了用于筛选细胞保护剂的试剂盒，其包括（1）Hsp90; （2）用于测定热休克蛋白表达诱导活性的试剂; （3）咪唑并噻嗪衍生物; 和（4）用于定量Hsp90客户蛋白质的试剂。
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公开(公告)号：US20090270326A1
公开(公告)日：2009-10-29
申请号：US12442091
申请日：2007-09-21
申请人： Haruhide Kimura
发明人： Haruhide Kimura
IPC分类号： A61K38/16 , C12N5/02 , A61K31/5415
CPC分类号： A61K31/5415 , A61K38/19
摘要： The present invention relates to an antioxidant response element (ARE) activator comprising a macrophage migration inhibitory factor (MIF) or a modified form thereof, an ARE activator comprising a combination of MIF or a modified form thereof and a substance capable of binding to MIF, and so on. These ARE activators are useful as safe and excellent cell death inhibitors, such as agents for the prevention/treatment of cardiovascular diseases, bone/joint diseases, infectious diseases, inflammatory diseases, renal diseases, central nervous system diseases, cancer or diabetes.
摘要翻译： 本发明涉及包含巨噬细胞迁移抑制因子（MIF）或其修饰形式的抗氧化应答元件（ARE）激活剂，包含MIF或其修饰形式的组合的ARE活化剂和能够结合MIF的物质， 等等。 这些ARE激活剂可用作安全和优异的细胞死亡抑制剂，例如用于预防/治疗心血管疾病，骨/关节疾病，感染性疾病，炎性疾病，肾脏疾病，中枢神经系统疾病，癌症或糖尿病的药物。
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公开(公告)号：US20090082343A1
公开(公告)日：2009-03-26
申请号：US12099779
申请日：2008-04-08
IPC分类号： A61K31/5415 , C07D401/04 , A61P9/00 , A61P1/00
CPC分类号： C07D417/04 , A61K31/5415 , C07D417/14
摘要： This invention provides a compound represented by the formula (I): wherein R1 is a hydrogen atom, a halogen atom, hydroxy, nitro, optionally halogenated alkyl, alkoxy optionally having substituents, acyl or amino optionally having substituents; R2 is pyridyl, furyl, thienyl, pyrrolyl, quinolyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, tetrahydroquinolyl or thiazolyl, each of which may have substituents; n is 1 or 2; or a salt. And this invention provides a safe pharmaceutical comprising the compound of the formula (I), which has an excellent apoptosis inhibitory effect and MIF binding effect, for preventing and/or treating heart disease, nervous degenerative disease, cerebrovascular disease, central nervous infectious disease, traumatorathy, demyelinating disease, bone and articular disease, kidney disease, liver disease, osteomyelodysplasia, AIDS, cancer, and the like.
摘要翻译： 本发明提供由式（I）表示的化合物：其中R1是氢原子，卤素原子，羟基，硝基，任选卤代烷基，任选具有取代基的烷氧基，任选具有取代基的酰基或氨基; R 2是可以具有取代基的吡啶基，呋喃基，噻吩基，吡咯基，喹啉基，吡嗪基，嘧啶基，哒嗪基，吲哚基，四氢喹啉基或噻唑基。 n为1或2; 或盐。 本发明提供了一种安全药物，其包含具有优异的细胞凋亡抑制作用和MIF结合作用的式（I）化合物，用于预防和/或治疗心脏病，神经退行性疾病，脑血管病，中枢神经感染性疾病， 外伤，脱髓鞘疾病，骨和关节疾病，肾脏疾病，肝病，骨发育不良，艾滋病，癌症等。
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7.发明授权公开(公告)号：US07659267B2
公开(公告)日：2010-02-09
申请号：US10537520
申请日：2003-12-04
IPC分类号： C07D279/16 , A61K31/5415
CPC分类号： C07D263/58 , A61K31/5415 , C07D279/08
摘要： As prophylactic and/or therapeutic agents for cardiovascular diseases, bone or joint diseases, infectious diseases, inflammatory diseases, kidney diseases, etc. having safe and excellent effects of cell death inhibition, MIF binding, etc., there are provided compounds represented by formula: [wherein, R1 represents a halogen atom, etc., R2 represents a group represented by formula: (wherein, R3 represents hydrogen atom, an optionally substituted alkoxy, etc., R4 represents hydrogen atom, bromine atom, cyano, etc., R5 represents hydrogen atom, hydroxy, etc., R6 represents hydrogen atom, etc., R7 represents hydrogen atom, etc.) etc., and n represents an integer of 0 to 4] or salts thereof.
摘要翻译： 作为具有安全且优异的细胞死亡抑制作用，MIF结合等的心血管疾病，骨或关节疾病，感染性疾病，炎性疾病，肾脏疾病等的预防和/或治疗剂，提供了式 [其中，R1表示卤素原子等，R2表示由式（其中R3表示氢原子，任选取代的烷氧基等，R4表示氢原子，溴原子，氰基等）表示的基团， R5表示氢原子，羟基等，R6表示氢原子等，R7表示氢原子等）等，n表示0〜4的整数]或其盐。
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8.发明授权Heart muscular cell apoptosis inhibitors and remedies/preventives for heart diseases 失效心脏肌细胞凋亡抑制剂和心脏病的治疗/预防药物公开(公告)号：US06794383B2
公开(公告)日：2004-09-21
申请号：US10363290
申请日：2003-02-27
IPC分类号： A61K315415
CPC分类号： C07D417/04 , A61K31/5415 , C07D279/08 , C07D279/16
摘要： The present invention is intended to provide excellent preventives and/or remedies for heart diseases. Specifically, the present invention provides heart muscle cell apoptosis inhibitors, preventives and/or remedies for heart diseases, comprising a compound represented by the following formula: wherein R represents an optionally substituted hydrocarbon group, an optionally substituted aromatic heterocyclic group, or an optionally substituted amino group; or a salt thereof.
摘要翻译： 本发明旨在为心脏病提供优异的预防措施和/或补救措施。 具体而言，本发明提供心肌细胞凋亡抑制剂，心脏病的预防剂和/或治疗药物，其包含由下式表示的化合物：其中R表示任选取代的烃基，任选取代的芳族杂环基或任选取代的 氨基; 或其盐。
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9.发明授权Cell death inhibition by macrophage migration inhibitory factor and a binding substance thereto 有权巨噬细胞迁移抑制因子及其结合物对细胞死亡的抑制作用公开(公告)号：US09044483B2
公开(公告)日：2015-06-02
申请号：US12442091
申请日：2007-09-21
申请人： Haruhide Kimura
发明人： Haruhide Kimura
IPC分类号： C07K14/52 , C07D279/04 , A61K31/5415 , A61K38/19
CPC分类号： A61K31/5415 , A61K38/19
摘要： The present invention relates to an antioxidant response element (ARE) activator comprising a macrophage migration inhibitory factor (MIF) or a modified form thereof, an ARE activator comprising a combination of MIF or a modified form thereof and a substance capable of binding to MIF, such as a 1,3-benzothiazinone, and so on. These ARE activators are useful.
摘要翻译： 本发明涉及包含巨噬细胞迁移抑制因子（MIF）或其修饰形式的抗氧化应答元件（ARE）激活剂，包含MIF或其修饰形式的组合的ARE活化剂和能够结合MIF的物质， 例如1,3-苯并噻嗪酮等。 这些ARE激活器是有用的。
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公开(公告)号：US20050032786A1
公开(公告)日：2005-02-10
申请号：US10488384
申请日：2002-09-02
IPC分类号： A61K31/5415 , A61P1/00 , A61P9/00 , A61P9/08 , A61P9/10 , A61P13/12 , A61P17/00 , A61P19/00 , A61P19/02 , A61P25/00 , A61P31/00 , A61P43/00 , C07D417/04 , C07D417/14 , C07D279/16
CPC分类号： C07D417/04 , A61K31/5415 , C07D417/14
摘要： This invention provides a compound represented by the formula (I): wherein R1 is a hydrogen atom, a halogen atom, hydroxy, nitro, optionally halogenated alkyl, alkoxy optionally having substituents, acyl or amino optionally having substituents; R2 is pyridyl, furyl, thienyl, pyrrolyl, quinolyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, tetrahydroquinolyl or thiazolyl, each of which may have substituents; n is 1 or 2; or a salt. And this invention provides a safe pharmaceutical comprising the compound of the formula (I), which has an excellent apoptosis inhibitory effect and MIF binding effect, for preventing and/or treating heart disease, nervous degenerative disease, cerebrovascular disease, central nervous infectious disease, traumatorathy, demyelinating disease, bone and articular disease, kidney disease, liver disease, osteomyelodysplasia, AIDS, cancer, and the like.
摘要翻译： 本发明提供由式（I）表示的化合物：其中R 1为氢原子，卤素原子，羟基，硝基，任选卤代烷基，任选具有取代基的烷氧基，任选具有取代基的酰基或氨基; R 2是吡啶基，呋喃基，噻吩基，吡咯基，喹啉基，吡嗪基，嘧啶基，哒嗪基，吲哚基，四氢喹啉基或噻唑基，其各自可以具有取代基; n为1或2; 或盐。 本发明提供一种安全药物，其包含具有优异的细胞凋亡抑制作用和MIF结合作用的式（I）化合物，用于预防和/或治疗心脏病，神经退行性疾病，脑血管病，中枢神经感染性疾病， 外伤，脱髓鞘疾病，骨和关节疾病，肾脏疾病，肝病，骨发育不良，艾滋病，癌症等。
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