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    RETINOID-ASSOCIATED RECEPTOR REGULATORS
    8.
    发明公开
    RETINOID-ASSOCIATED RECEPTOR REGULATORS 审中-公开
    RETINOIDASSOZIIERTE REGULATOREN VON REZEPTOREN

    公开(公告)号：EP1092711A1

    公开(公告)日：2001-04-18

    申请号：EP99926853.5

    申请日：1999-06-30

    申请人： Takeda Chemical Industries, Ltd.

    发明人： SUGIYAMA, Yasuo ,  MOMOSE, Yu ,  KIMURA, Hiroyuki ,  SAKAMOTO, Junichi ,  ODAKA, Hiroyuki

    IPC分类号： C07D263/30 ,  C07D277/30 ,  C07D413/04 ,  C07D417/04 ,  A61K31/42 ,  A61K31/425 ,  A61K31/44

    CPC分类号： C07D413/04 ,  C07D263/32 ,  C07D277/30 ,  C07D417/04

    摘要： A pharmaceutical composition of the invention which is a retinoid-related receptor function regulating agent comprising a 1,3-azole derivative represented by formula (I):
    wherein R 1 is an aromatic hydrocarbon group or an aromatic heterocyclic group, each of which may be substituted; R 2 is hydrogen or an optionally substituted hydrocarbon group; X is O, S or a group represented by the formula: -NR 4 - wherein R 4 is hydrogen or an optionally substituted alkyl group; A is an aromatic hydrocarbon group or an aromatic heterocyclic group, each of which may be substituted; R 3 is a group represented by the formula: -OR 5 wherein R 5 is hydrogen or an optionally substituted hydrocarbon group, or -NR 6 R 7 wherein R 6 and R 7 are same or different and each is hydrogen or an optionally substituted hydrocarbon group, or R 6 and R 7 may be taken together with an adjacent nitrogen atom to form a ring, provided that compounds represented by the formulae:

    are excluded, or its salt, is low in toxicity, and can be employed, for instance, as an agent for preventing or treating diabetes (e.g., insulin-dependent diabetes, non-insulin-dependent diabetes, gestational diabetes), an agent for preventing or treating hyperlipidemia (e.g., hypertriglyceridemia, hypercholesterolemia, hypo-HDL-cholesterolemia), an insulin sensitivity enhancing agent, an insulin resistance improving agent, an agent for preventing or treating impaired glucose tolerance (IGT), and an agent for preventing transition from impaired glucose tolerance to diabetes.
    Further, a pharmaceutical composition of the invention can be used, for instance, as an agent for preventing or treating diabetic complications (e.g., neuropathy, nephropathy, retinopathy, cataract, macroangiopathy, osteopenia), obesity, osteoporosis, cachexia (e.g., carcinomatous cachexia, tuberculous cachexia, diabetic cachexia, hemopathic cachexia, endocrinopathic cachexia, infectious cachexia or cachexia induced by acquired immunodeficiency syndrome), fatty liver, hypertension, polycystic ovary syndrome, renal diseases (e.g., diabetic nephropathy, glomerular nephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, terminal renal disorder), muscular dystrophy, myocardiac infarction, angina pectoris, cerebral infarction, insulin resistant syndrome, syndrome X, hyperinsulinemia-induced sensory disorder, tumor (e.g., leukemia, breast cancer, prostate cancer, skin cancer), arteriosclerosis (e.g., atherosclerosis) and as a pharmaceutical for controlling appetite or food intake.

    摘要翻译： 本发明的药物组合物，其为类视黄醇相关受体功能调节剂，其包含由式（I）表示的1,3-唑衍生物：其中R 1为芳族烃基或芳族杂环基， 每个可以被替代; R 2是氢或任选取代的烃基; X是O，S或由下式表示的基团-NR 4 - ，其中R 4是氢或任选取代的烷基; A是芳族烃基或芳族杂环基，其各自可以被取代; R 3是由下式表示的基团：-OR 5其中R 5是氢或任选取代的烃基，或-NR 6 R 7，其中R 6和R 7 >相同或不同，各自为氢或任选取代的烃基，或者R 6和R 7可以与相邻的氮原子一起形成环，条件是由下式表示的化合物： 被排除，或其盐，毒性低，可用于例如预防或治疗糖尿病的药物（例如，胰岛素依赖性糖尿病，非胰岛素依赖型糖尿病，妊娠糖尿病） ，用于预防或治疗高脂血症（例如高甘油三酯血症，高胆固醇血症，低HDL-胆固醇血症），胰岛素敏感性增强剂，胰岛素抵抗改善剂，用于预防或治疗葡萄糖耐量降低的药剂（IGT）的药剂，以及药剂 用于防止糖耐量受损转变为糖尿病。 此外，本发明的药物组合物可以用作例如糖尿病并发症（例如神经病，肾病，视网膜病变，白内障，大血管病变，骨质减少症），肥胖症，骨质疏松症，恶病质（如恶病质性恶病质 ，结核性恶病质，糖尿病性恶病质，血液恶病质，内分泌性恶病质，感染性恶病质或获得性免疫缺陷综合征引起的恶病质），脂肪肝，高血压，多囊卵巢综合征，肾脏疾病（例如，糖尿病性肾病，肾小球肾炎，肾小球硬化，肾病综合征，高血压 肾病，末期肾功能障碍），肌营养不良症，心肌梗死，心绞痛，脑梗塞，胰岛素抵抗综合征，综合征X，高胰岛素血症诱导的感觉障碍，肿瘤（如白血病，乳腺癌，前列腺癌，皮肤癌），动脉硬化 例如动脉粥样硬化）和作为控制食欲的药物o r食物摄入。