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    8-AZAPROSTAGLANDIN DERIVATIVES AND MEDICAL USE THEREOF
    1.
    发明申请
    8-AZAPROSTAGLANDIN DERIVATIVES AND MEDICAL USE THEREOF 审中-公开
    8-AZAPROSTAGLANDIN衍生物及其医疗用途

    公开(公告)号：US20080033033A1

    公开(公告)日：2008-02-07

    申请号：US11749531

    申请日：2007-05-16

    申请人： Tohru Kambe ,  Toru Maruyama ,  Kaoru Kobayashi ,  Kousuke Tani ,  Yoshihiko Nakai ,  Toshihiko Nagase ,  Takayuki Maruyama ,  Kiyoto Sakata ,  Hideyuki Yoshida ,  Shinsei Fujimura ,  Akio Nishiura ,  Nobutaka Abe

    发明人： Tohru Kambe ,  Toru Maruyama ,  Kaoru Kobayashi ,  Kousuke Tani ,  Yoshihiko Nakai ,  Toshihiko Nagase ,  Takayuki Maruyama ,  Kiyoto Sakata ,  Hideyuki Yoshida ,  Shinsei Fujimura ,  Akio Nishiura ,  Nobutaka Abe

    IPC分类号： A61K31/41 ,  A61K31/4015 ,  C07D207/18 ,  C07D257/04

    CPC分类号： C07D417/12 ,  C07D417/14

    摘要： The pharmaceutical composition comprising the compound of the invention having 8-azaprostaglandin skeleton represented by formula (I) (wherein, all the symbols have the same meanings as that of the specification.) a salt thereof, a solvate thereof or a cyclodextrin clathrate thereof, or a prodrug thereof and them as active ingredient have EP4 agonistic action and thus are considered useful for the prevention and/or treatment of immunological diseases, asthma, neuronal cell death, arthritis, lung failure, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardial ischemia, systemic inflammatory response syndrome, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, shock and glaucoma, etc. Furthermore, the compounds also have an action of accelerating bone formation, so it is expected to be useful for the prevention and/or treatment of diseases associated with loss in bone mass, for example, primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss, osteonecrosis, bone formation after bone operation, alternative treatment for bone grafting.

    摘要翻译： 包含本发明化合物的盐，其盐，其溶剂合物或环糊精包合物，其具有由式（I）表示的8-氮杂前列腺素骨架（其中所有符号具有与说明书相同的含义） 或其前药，并且它们作为活性成分具有EP 4激动作用，因此被认为可用于预防和/或治疗免疫疾病，哮喘，神经元细胞死亡，关节炎，肺衰竭，肺纤维化 ，肺气肿，支气管炎，慢性阻塞性肺疾病，肝损伤，急性肝炎，肾炎，肾功能不全，高血压，心肌缺血，全身炎症反应综合征，败血症，血液综合征，巨噬细胞活化综合征，静脉炎，川崎病，烧伤，系统性 肉芽肿病，溃疡性结肠炎，克罗恩病，透析中的高细胞因子血症，多器官功能衰竭，休克和青光眼等。 此外，化合物还具有促进骨形成的作用，因此预期可用于预防和/或治疗与骨量丧失相关的疾病，例如原发性骨质疏松症，继发性骨质疏松症，癌症的骨转移， 高钙血症，佩吉特氏病，骨丢失，骨坏死，骨手术后的骨形成，骨移植的替代治疗。

    8-azaprostaglandin derivatives and medical use thereof
    4.
    发明授权
    8-azaprostaglandin derivatives and medical use thereof 失效
    8-氮杂普罗兰前列腺素衍生物及其医疗用途

    公开(公告)号：US07256211B1

    公开(公告)日：2007-08-14

    申请号：US10542724

    申请日：2004-01-20

    申请人： Tohru Kambe ,  Toru Maruyama ,  Kaoru Kobayashi ,  Kousuke Tani ,  Yoshihiko Nakai ,  Toshihiko Nagase ,  Takayuki Maruyama ,  Kiyoto Sakata ,  Hideyuki Yoshida ,  Shinsei Fujimura ,  Akio Nishiura ,  Nobutaka Abe

    发明人： Tohru Kambe ,  Toru Maruyama ,  Kaoru Kobayashi ,  Kousuke Tani ,  Yoshihiko Nakai ,  Toshihiko Nagase ,  Takayuki Maruyama ,  Kiyoto Sakata ,  Hideyuki Yoshida ,  Shinsei Fujimura ,  Akio Nishiura ,  Nobutaka Abe

    IPC分类号： A61K31/40 ,  A61K31/426 ,  C07D207/12 ,  C07D207/36

    CPC分类号： C07D417/12 ,  C07D417/14

    摘要： The pharmaceutical composition comprising the compound of the invention having 8-azaprostaglandin skeleton represented by formula (I) (wherein, all the symbols have the same meanings as that of the specification) a salt thereof, a solvate thereof or a cyclodextrin clathrate thereof, or a prodrug thereof and them as active ingredient have EP4 agonistic action and thus are considered useful for the prevention and/or treatment of immunological diseases, asthma, neuronal cell death, arthritis, lung failure, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardial ischemia, systemic inflammatory response syndrome, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, shock and glaucoma, etc. Furthermore, the compounds also have an action of accelerating bone formation, so it is expected to be useful for the prevention and/or treatment of diseases associated with loss in bone mass, for example, primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss, osteonecrosis, bone formation after bone operation, alternative treatment for bone grafting.

    摘要翻译： 该药物组合物包含本发明化合物，其具有式（I）表示的8-氮杂前列腺素骨架（其中所有符号具有与说明书相同的含义）其盐，其溶剂合物或环糊精包合物，或 其前药和它们作为活性成分具有EP 4激动作用，因此被认为可用于预防和/或治疗免疫疾病，哮喘，神经元细胞死亡，关节炎，肺衰竭，肺纤维化， 肺气肿，支气管炎，慢性阻塞性肺疾病，肝损伤，急性肝炎，肾炎，肾功能不全，高血压，心肌缺血，全身炎症反应综合征，败血症，血液综合征，巨噬细胞活化综合征，Still氏病，川崎病，烧伤，全身性肉芽肿病 ，溃疡性结肠炎，克罗恩病，透析中的高细胞因子血症，多器官功能衰竭，休克和青光眼等。 该化合物还具有加速骨形成的作用，因此预期可用于预防和/或治疗与骨质量损失相关的疾病，例如原发性骨质疏松症，继发性骨质疏松症，癌症的骨转移， 高钙血症，佩吉特氏病，骨丢失，骨坏死，骨手术后的骨形成，骨移植的替代治疗。

    8-azaprostaglandin derivative compound and agent comprising the compound as active ingredient
    7.
    发明授权
    8-azaprostaglandin derivative compound and agent comprising the compound as active ingredient 失效
    8-氮杂的前列腺素衍生物化合物和包含该化合物作为活性成分的试剂

    公开(公告)号：US08026273B2

    公开(公告)日：2011-09-27

    申请号：US12683609

    申请日：2010-01-07

    申请人： Kousuke Tani ,  Kaoru Kobayashi ,  Toru Maruyama ,  Tohru Kambe ,  Mikio Ogawa ,  Tsutomu Shiroya

    发明人： Kousuke Tani ,  Kaoru Kobayashi ,  Toru Maruyama ,  Tohru Kambe ,  Mikio Ogawa ,  Tsutomu Shiroya

    IPC分类号： A61K31/40 ,  A61K31/405 ,  C07D207/00 ,  C07D209/00

    CPC分类号： C07D413/06 ,  C07D207/26 ,  C07D263/24 ,  C07D405/06 ,  C07D405/12 ,  C07D409/06 ,  C07D409/12 ,  C07D413/12 ,  C07D417/06 ,  C07D417/12

    摘要： An 8-azaprostaglandin represented by formula (I) (wherein all symbols have the same meanings as described in the specification), a pharmaceutically acceptable salt thereof or a cyclodextrin clathrate thereof. Since the compound represented by formula (I) binds to EP2 subtype among PGE receptor strongly, it is useful for preventive and/or treatment for immune diseases, allergic diseases, neuronal cell death, dysmenorrhea, premature birth, abortion, baldness, retinal neuropathy such as glaucoma, erectile dysfunction, arthritis, pulmonary injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, hepatic injury, acute hepatitis, liver cirrhosis, shock, nephritis, renal failure, circulatory diseases, systemic inflammatory response syndrome, sepsis, hemophagocytosis syndrome, macrophage activation syndrome, still disease, Kawasaki Disease, burn, systemic granuloma, ulcerative colitis, Crohn disease, hypercytokinemia at dialysis, multiple organ failure, or bone diseases etc.

    摘要翻译： 由式（I）（其中所有符号具有与说明书中所述相同的含义）表示的8-氮杂前列腺素，其药学上可接受的盐或其环糊精包合物。 由于式（I）表示的化合物强烈地与PGE受体中的EP2亚型结合，因此可用于免疫疾病，过敏性疾病，神经元细胞死亡，痛经，早产，流产，秃发，视网膜神经病变等的预防和/或治疗 青光眼，勃起功能障碍，关节炎，肺损伤，肺纤维化，肺气肿，支气管炎，慢性阻塞性肺病，肝损伤，急性肝炎，肝硬化，休克，肾炎，肾衰竭，循环系统疾病，全身性炎症反应综合征，败血症， 血细胞增多综合征，巨噬细胞活化综合征，静止病，川崎病，烧伤，全身肉芽肿，溃疡性结肠炎，克罗恩病，透析中的高细胞因子血症，多器官功能衰竭或骨骼疾病等。

    8-AZAPROSTAGLANDIN DERIVATIVE COMPOUND AND AGENT COMPRISING THE COMPOUND AS ACTIVE INGREDIENT
    9.
    发明申请
    8-AZAPROSTAGLANDIN DERIVATIVE COMPOUND AND AGENT COMPRISING THE COMPOUND AS ACTIVE INGREDIENT 失效
    8-AZAPROSTAGLANDIN衍生化合物和包含化合物作为活性成分的试剂

    公开(公告)号：US20100113388A1

    公开(公告)日：2010-05-06

    申请号：US12683609

    申请日：2010-01-07

    申请人： Kousuke Tani ,  Kaoru Kobayashi ,  Toru Maruyama ,  Tohru Kambe ,  Mikio Ogawa ,  Tsutomu Shiroya

    发明人： Kousuke Tani ,  Kaoru Kobayashi ,  Toru Maruyama ,  Tohru Kambe ,  Mikio Ogawa ,  Tsutomu Shiroya

    IPC分类号： A61K31/724 ,  A61K31/427 ,  A61K31/422 ,  A61K31/4015 ,  C07D277/36 ,  C07D263/32 ,  C07D207/46 ,  A61P19/08 ,  A61P1/04 ,  A61P17/14

    CPC分类号： C07D413/06 ,  C07D207/26 ,  C07D263/24 ,  C07D405/06 ,  C07D405/12 ,  C07D409/06 ,  C07D409/12 ,  C07D413/12 ,  C07D417/06 ,  C07D417/12

    摘要： An 8-azaprostaglandin represented by formula (I) (wherein all symbols have the same meanings as described in the specification), a pharmaceutically acceptable salt thereof or a cyclodextrin clathrate thereof. Since the compound represented by formula (I) binds to EP2 subtype among PGE receptor strongly, it is useful for preventive and/or treatment for immune diseases, allergic diseases, neuronal cell death, dysmenorrhea, premature birth, abortion, baldness, retinal neuropathy such as glaucoma, erectile dysfunction, arthritis, pulmonary injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, hepatic injury, acute hepatitis, liver cirrhosis, shock, nephritis, renal failure, circulatory diseases, systemic inflammatory response syndrome, sepsis, hemophagocytosis syndrome, macrophage activation syndrome, still disease, Kawasaki Disease, burn, systemic granuloma, ulcerative colitis, Crohn disease, hypercytokinemia at dialysis, multiple organ failure, or bone diseases etc.

    摘要翻译： 由式（I）（其中所有符号具有与说明书中所述相同的含义）表示的8-氮杂前列腺素，其药学上可接受的盐或其环糊精包合物。 由于式（I）表示的化合物强烈地与PGE受体中的EP2亚型结合，因此可用于免疫疾病，过敏性疾病，神经元细胞死亡，痛经，早产，流产，秃发，视网膜神经病变等的预防和/或治疗 青光眼，勃起功能障碍，关节炎，肺损伤，肺纤维化，肺气肿，支气管炎，慢性阻塞性肺病，肝损伤，急性肝炎，肝硬化，休克，肾炎，肾衰竭，循环系统疾病，全身性炎症反应综合征，败血症， 血细胞增多综合征，巨噬细胞活化综合征，静止病，川崎病，烧伤，全身肉芽肿，溃疡性结肠炎，克罗恩病，透析中的高细胞因子血症，多器官功能衰竭或骨骼疾病等。

    8-azaprostaglandin derivative compound and agent comprising the compound as active ingredient
    10.
    发明授权
    8-azaprostaglandin derivative compound and agent comprising the compound as active ingredient 失效
    8-氮杂的前列腺素衍生物化合物和包含该化合物作为活性成分的试剂

    公开(公告)号：US07683094B2

    公开(公告)日：2010-03-23

    申请号：US12139260

    申请日：2008-06-13

    申请人： Kousuke Tani ,  Kaoru Kobayashi ,  Toru Maruyama ,  Tohru Kambe ,  Mikio Ogawa ,  Tsutomu Shiroya

    发明人： Kousuke Tani ,  Kaoru Kobayashi ,  Toru Maruyama ,  Tohru Kambe ,  Mikio Ogawa ,  Tsutomu Shiroya

    IPC分类号： A61K31/40 ,  C07D207/00

    CPC分类号： C07D413/06 ,  C07D207/26 ,  C07D263/24 ,  C07D405/06 ,  C07D405/12 ,  C07D409/06 ,  C07D409/12 ,  C07D413/12 ,  C07D417/06 ,  C07D417/12

    摘要： An 8-azaprostaglandin represented by formula (I) (wherein all symbols have the same meanings as described in the specification), a pharmaceutically acceptable salt thereof or a cyclodextrin clathrate thereof. Since the compound represented by formula (I) binds to EP2 subtype among PGE receptor strongly, it is useful for preventive and/or treatment for immune diseases, allergic diseases, neuronal cell death, dysmenorrhea, premature birth, abortion, baldness, retinal neuropathy such as glaucoma, erectile dysfunction, arthritis, pulmonary injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, hepatic injury, acute hepatitis, liver cirrhosis, shock, nephritis, renal failure, circulatory diseases, systemic inflammatory response syndrome, sepsis, hemophagocytosis syndrome, macrophage activation syndrome, still disease, Kawasaki Disease, burn, systemic granuloma, ulcerative colitis, Crohn disease, hypercytokinemia at dialysis, multiple organ failure, or bone diseases etc.

    摘要翻译： 由式（I）（其中所有符号具有与说明书中所述相同的含义）表示的8-氮杂前列腺素，其药学上可接受的盐或其环糊精包合物。 由于式（I）表示的化合物强烈地与PGE受体中的EP2亚型结合，因此可用于免疫疾病，过敏性疾病，神经元细胞死亡，痛经，早产，流产，秃发，视网膜神经病变等的预防和/或治疗 青光眼，勃起功能障碍，关节炎，肺损伤，肺纤维化，肺气肿，支气管炎，慢性阻塞性肺病，肝损伤，急性肝炎，肝硬化，休克，肾炎，肾衰竭，循环系统疾病，全身性炎症反应综合征，败血症， 血细胞增多综合征，巨噬细胞活化综合征，静止病，川崎病，烧伤，全身肉芽肿，溃疡性结肠炎，克罗恩病，透析中的高细胞因子血症，多器官功能衰竭或骨骼疾病等。