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    Hexahydro-5-imino-1,4-heteroazepine derivatives as inhibitors of nitric oxide synthases
    1.
    发明授权
    Hexahydro-5-imino-1,4-heteroazepine derivatives as inhibitors of nitric oxide synthases 失效
    六氢-5-亚氨基-1,4-异吖啶衍生物作为一氧化氮合酶的抑制剂

    公开(公告)号：US6043358A

    公开(公告)日：2000-03-28

    申请号：US721784

    申请日：1996-09-25

    申请人： Charles G. Caldwell ,  William K. Hagmann ,  Malcolm Maccoss ,  Shrenik K. Shah ,  Kothandaraman Shankaran ,  Karla L. Furman

    发明人： Charles G. Caldwell ,  William K. Hagmann ,  Malcolm Maccoss ,  Shrenik K. Shah ,  Kothandaraman Shankaran ,  Karla L. Furman

    IPC分类号： A61P15/10 ,  C07D243/08 ,  C07D267/16 ,  C07D281/06 ,  C07D337/04 ,  C07D267/10 ,  C07D267/12 ,  C07D267/14

    CPC分类号： C07D281/06 ,  C07D243/08 ,  C07D267/16 ,  C07D337/04

    摘要： Disclosed herein are compounds of Formula I and pharmaceutically acceptable salts thereof which have been found useful in the treatment of nitric oxide synthase mediated diseases and disorders, including neurodegenerative disorders, disorders of gastrointestinal motility and inflammation. These diseases and disorders include hypotension, septic shock, toxic shock syndrome, hemodialysis, IL-2 therapy such as in in cancer patients, cachexia, immunosuppression such as in transplant therapy, autoimmune and/or inflammatory indications including sunburn, eczema or psoriasis and respiratory conditions such as bronchitis, asthma, oxidant-induced lung injury and acute respiratory distress (ARDS), glomerulonephritis, restenosis, inflammatory sequelae of viral infections, myocarditis, heart failure, atherosclerosis, osteoarthritis, rheumatoid arthritis, septic arthritis, chronic or inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic lupus erythematosis (SLE), ocular conditions such as ocular hypertension, retinitis and uveitis, type 1 diabetes, insulin-dependent diabetes mellitus and cystic fibrosis.

    摘要翻译： 本文公开了已经发现可用于治疗一氧化氮合酶介导的疾病和病症的式I化合物及其药学上可接受的盐，所述疾病和病症包括神经变性疾病，胃肠蠕动和炎症病症。 这些疾病和障碍包括低血压，脓毒性休克，中毒性休克综合征，血液透析，诸如癌症患者中的IL-2治疗，恶病质，免疫抑制如移植治疗，自身免疫和/或炎性指征，包括晒伤，湿疹或银屑病和呼吸 诸如支气管炎，哮喘，氧化剂诱发的肺损伤和急性呼吸窘迫（ARDS），肾小球性肾炎，再狭窄，病毒感染的炎症后遗症，心肌炎，心力衰竭，动脉粥样硬化，骨关节炎，类风湿性关节炎，脓毒性关节炎，慢性或炎性肠病 溃疡性结肠炎，克罗恩病，系统性红斑狼疮（SLE），眼部疾病如眼高压，视网膜炎和葡萄膜炎，1型糖尿病，胰岛素依赖性糖尿病和囊性纤维化。

    Hexahydro-5-imino-1,4-1,4-thiazepine derivatives as inhibitors of nitric oxide synthases
    2.
    发明授权
    Hexahydro-5-imino-1,4-1,4-thiazepine derivatives as inhibitors of nitric oxide synthases 失效
    六氢-5-亚氨基-1,4-1,4-硫杂衍生物作为一氧化氮合酶的抑制剂

    公开(公告)号：US06372733B1

    公开(公告)日：2002-04-16

    申请号：US09477246

    申请日：2000-01-04

    申请人： Charles G. Caldwell ,  Malcolm Maccoss ,  William K. Hagmann ,  Shrenik K. Shah ,  Kothandaraman Shankaran ,  Karla L. Furman

    发明人： Charles G. Caldwell ,  Malcolm Maccoss ,  William K. Hagmann ,  Shrenik K. Shah ,  Kothandaraman Shankaran ,  Karla L. Furman

    IPC分类号： C07D2806

    CPC分类号： C07D281/06 ,  C07D243/08 ,  C07D267/16 ,  C07D337/04

    摘要： Disclosed herein are compounds of Formula I and pharmaceutically acceptable salts thereof which have been found useful in the treatment of nitric oxide synthase mediated diseases and disorders, including neurodegenerative disorders, disorders of gastrointestinal motility and inflammation. These diseases and disorders include hypotension, septic shock, toxic shock syndrome, hemodialysis, IL-2 therapy such as in in cancer patients, cachexia, immunosuppression such as in transplant therapy, autoimmune and/or inflammatory indications including sunburn, eczema or psoriasis and respiratory conditions such as bronchitis, asthma, oxidant-induced lung injury and acute respiratory distress (ARDS), glomerulonephritis, restenosis, inflammatory sequelae of viral infections, myocarditis, heart failure, atherosclerosis, osteoarthritis, rheumatoid arthritis, septic arthritis, chronic or inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic lupus erythematosis (SLE), ocular conditions such as ocular hypertension, retinitis and uveitis, type 1 diabetes, insulin-dependent diabetes mellitus and cystic fibrosis.

    摘要翻译： 本发明公开了已发现可用于治疗一氧化氮合酶介导的疾病和病症（包括神经退行性疾病，胃肠蠕动和炎症病症）的式I化合物及其药学上可接受的盐。 这些疾病和障碍包括低血压，脓毒性休克，中毒性休克综合征，血液透析，诸如癌症患者中的IL-2治疗，恶病质，免疫抑制如移植治疗，自身免疫和/或炎性指征，包括晒伤，湿疹或银屑病和呼吸 诸如支气管炎，哮喘，氧化剂诱发的肺损伤和急性呼吸窘迫（ARDS），肾小球性肾炎，再狭窄，病毒感染的炎症后遗症，心肌炎，心力衰竭，动脉粥样硬化，骨关节炎，类风湿性关节炎，脓毒性关节炎，慢性或炎性肠病 溃疡性结肠炎，克罗恩病，系统性红斑狼疮（SLE），眼部疾病如眼高压，视网膜炎和葡萄膜炎，1型糖尿病，胰岛素依赖性糖尿病和囊性纤维化。

    Substituted N-carboxyalkylpeptidyl derivatives as antidegenerative active agents
    7.
    发明授权
    Substituted N-carboxyalkylpeptidyl derivatives as antidegenerative active agents 失效
    取代的N-羧基烷基肽基衍生物作为抗再生活性剂

    公开(公告)号：US5932551A

    公开(公告)日：1999-08-03

    申请号：US848766

    申请日：1997-05-01

    申请人： Charles G. Caldwell ,  Kevin T. Chapman ,  Craig K. Esser ,  William K. Hagmann ,  Ihor E. Kopka ,  Scott A. Polo ,  Soumya P. Sahoo ,  Philippe L. Durette

    发明人： Charles G. Caldwell ,  Kevin T. Chapman ,  Craig K. Esser ,  William K. Hagmann ,  Ihor E. Kopka ,  Scott A. Polo ,  Soumya P. Sahoo ,  Philippe L. Durette

    IPC分类号： A61K38/00 ,  C07K5/02 ,  A61K38/05

    CPC分类号： C07K5/022 ,  A61K38/00

    摘要： Novel N-carboxyalkylpeptidyl compounds of formula I are found to be useful inhibitors of matrix metalloendoproteinase-mediated diseases including osteoarthritis, rheumatoid arthritis, septic arthritis, tumor invasion in certain cancers, periodontal disease, corneal ulceration, proteinuria, dystrophobic epidermolysis bullosa, and coronary thrombosis associated with atherosclerotic plaque rupture. The matrix metalloendoproteinases are a family of zinc-containing proteinases including but not limited to stromelysin, collagenase, and gelatinase, that are capable of degrading the major components of articular cartilage and basement membranes. The inhibitors claimed herein may also be useful in preventing the pathological sequelae following a traumatic injury that could lead to a permanent disability. These compounds may also have utility as a means for birth control by preventing ovulation or implantation. ##STR1##

    摘要翻译： 发现式I的新型N-羧基烷基肽基化合物是有用的基质金属蛋白酶介导的疾病的抑制剂，包括骨关节炎，类风湿性关节炎，脓毒性关节炎，某些癌症中的肿瘤侵袭，牙周病，角膜溃疡，蛋白尿，疏水性表皮松解性大疱性和冠状动脉血栓形成 与动脉粥样硬化斑块破裂有关。 基质金属蛋白酶是含有蛋白酶的家族，其包括但不限于基质溶素，胶原酶和明胶酶，其能够降解关节软骨和基底膜的主要成分。 本文所要求的抑制剂也可用于预防可能导致永久性残疾的外伤性损伤后的病理后遗症。 这些化合物也可以通过预防排卵或植入作为避孕的手段。