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    Tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidines as integrin antagonists
    4.
    发明授权
    Tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidines as integrin antagonists 失效
    四氢异喹啉-3-羧酸烷氧基胍作为整联蛋白拮抗剂

    公开(公告)号：US06486174B2

    公开(公告)日：2002-11-26

    申请号：US09969181

    申请日：2001-10-03

    申请人： Aihua Wang ,  David C. U'Prichard ,  Victor J. Marder

    发明人： Aihua Wang ,  David C. U'Prichard ,  Victor J. Marder

    IPC分类号： C07D21700

    CPC分类号： C07D401/12 ,  C07D217/26

    摘要： The present invention relates to novel tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidine compounds that are antagonists of alpha V (&agr;v) integrins, for example &agr;v&bgr;3 and &agr;v&bgr;5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment and/or prevention of pathological conditions mediated by &agr;v&bgr;3 and &agr;v&bgr;5 integrins such as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, rheumatoid arthritis, sickle cell anemia, and in treatment and/or prevention of central nervous system (CNS) related disorders such as neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia, surgery, neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, adverse consequences of overstimulation of one or more excitatory amino acids, anxiety, convulsions, chronic pain, psychosis, schizophrenia, anesthesia, and opiate tolerance. The compounds have the general formula: where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, m and n are defined herein.

    摘要翻译： 本发明涉及作为αV（alphav）整联蛋白的拮抗剂的新型四氢异喹啉-3-羧酸烷氧基胍化合物，例如阿尔法博3和阿尔法肽5整联蛋白，其药学上可接受的盐及其药物组合物。 该化合物可用于治疗和/或预防由α1和α2融合素如肿瘤生长，转移，再狭窄，骨质疏松症，炎症，黄斑变性，糖尿病性视网膜病变，类风湿性关节炎，镰状细胞性贫血和治疗中介导的病理状况 和/或预防中枢神经系统（CNS）相关疾病，例如与中风，缺血，CNS创伤，低血糖症，手术，神经变性疾病如阿尔茨海默病和帕金森病相关的神经元损失，过度刺激一种或多种兴奋剂的不良后果 氨基酸，焦虑，抽搐，慢性疼痛，精神病，精神分裂症，麻醉和阿片剂耐受。 这些化合物具有以下通式：其中R1，R2，R3，R4，R5，R6，R7，R8，R9，R10，m和n如本文所定义。

    Assay for soluble crosslinked fibrin polymers
    5.
    发明授权
    Assay for soluble crosslinked fibrin polymers 失效
    测定可溶性交联纤维蛋白聚合物

    公开(公告)号：US5206140A

    公开(公告)日：1993-04-27

    申请号：US499250

    申请日：1990-03-26

    申请人： Victor J. Marder ,  Charles W. Francis

    发明人： Victor J. Marder ,  Charles W. Francis

    IPC分类号： C12Q1/56 ,  G01N33/86

    CPC分类号： G01N33/86 ,  C12Q1/56 ,  G01N2333/75 ,  G01N2333/9726

    摘要： This invention relates to an assay for fibrin polymers for use in the diagnosis of patients at risk of thrombosis and in monitoring the effects of treatment in such patients. More particularly, the present invention relates to an assay for soluble crosslinked fibrin polymers in patent samples involving the in vitro treatment of the sample with a proteolytic enzyme such as t-PA which generates the D-dimer fragment of soluble fibrin polymers. The amount of D-dimer formed is determined by an immunoassay specific for D-dimer. The measurement of D-dimer is thus a useful reflection of the hypercoagulability state and the test may be useful for assessing pre-thrombotic or thrombotic disorders such as myocardial infarction, pulmonary embolism and deep vein thrombosis, as well as for soluble fibrin formation in neoplastic, immune, inflammatory states, or other pathologic conditions, and for evaluations of therapy such as with anticoagulants that are used to treat these conditions.

    摘要翻译： 本发明涉及用于诊断患有血栓形成风险的患者和用于监测这些患者的治疗效果的纤维蛋白聚合物的测定。 更具体地，本发明涉及专利样品中可溶性交联纤维蛋白聚合物的测定法，其涉及用蛋白水解酶例如t-PA体外处理样品，其产生可溶性纤维蛋白聚合物的D-二聚体片段。 通过对D-二聚体特异性的免疫测定来测定形成的D-二聚体的量。 因此，D-二聚体的测量是高凝状态的有用反映，并且该测试可用于评估预先血栓形成或血栓形成障碍，例如心肌梗塞，肺栓塞和深静脉血栓形成，以及在肿瘤中可溶性纤维蛋白形成 ，免疫，炎症状态或其他病理状况，以及用于治疗的评估，例如用于治疗这些病症的抗凝剂。