3-[adamantan-1-yl]-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine | 327093-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吖庚因类
• 英文名称: 3-[adamantan-1-yl]-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine
• 英文别名: 3-(1-adamantyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine
• CAS: 327093-42-5
• 化学式: C₁₇H₂₅N₃
• 分子量: 271.406
• InChiKey: VFTQRHWULYJKCI-UHFFFAOYSA-N

物化性质

• 沸点：
  452.3±28.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  己内酰胺 以 二氯甲烷 、 甲苯 为溶剂， 生成 3-[adamantan-1-yl]-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine
  参考文献：
  名称：

  Adamantyl triazoles as selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1

  摘要：

  Adamantyl triazoles were identified as selective inhibitors of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). They are active both in in vitro and in in vivo pharmacodynamic models. The synthesis and structure-activity relationships of these inhibitors are presented. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.040

文献信息

• 11-Beta-hydroxysteroid dehydrogenase 1 inhibitors useful for the treatment of diabetes, obesity and dyslipidemia
  申请人：Balkovec M. James

  公开号：US20050070720A1

  公开（公告）日：2005-03-31

  Compounds having Formula (I), including pharmaceutically acceptable salts and prodrugs thereof: are selective inhibitors of the 11β-HSD1 enzyme. They inhibit the 11β-HSD1-mediated conversion of cortisone and other 11-keto-glucocorticoids to cortisol and other 11β-hydroxy-glucocorticoids. The 11β-HSD1 inhibitors therefore decrease the amount of cortisol in target tissues, thereby modulating the effects of cortisol. Modulation of cortisol may be effective in controlling non-insulin-dependent diabetes (NIDDM), hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, Syndrome X, and other symptoms associated with NIDDM or with excess cortisol in the body.

  化合物公式为（I）的化合物，包括其药学上可接受的盐和前药：是11β-HSD1酶的选择性抑制剂。它们抑制11β-HSD1介导的可的松和其他11-酮基-糖皮质激素转化为皮质醇和其他11β-羟基-糖皮质激素的过程。因此，11β-HSD1抑制剂减少了目标组织中皮质醇的含量，从而调节了皮质醇的效应。调节皮质醇可能对控制非胰岛素依赖性糖尿病（NIDDM）、高血糖、肥胖症、胰岛素抵抗、血脂异常、高脂血症、高血压、X综合征和与体内过多皮质醇有关的其他症状有效。
• Pharmaceutical combination of an aldosterone synthase inhibitor and a glucocorticoid receptor antagonist or a cortisol synthesis inhibitor or a corticotropin releasing factor antagonist
  申请人：Speedel Experimenta AG

  公开号：EP1886695A1

  公开（公告）日：2008-02-13

  The invention relates to a pharmaceutical combination comprising (a) an aldosterone synthase inhibitor or a pharmaceutically acceptable salt thereof, and (b) a glucocorticoid receptor antagonist or a cortisol synthesis inhibitor or a cortisol re-synthesis inhibitor or a corticotrophin-releasing hormone receptor antagonist or combinations thereof or in each case a pharmaceutically acceptable salt thereof. Said composition is useful for the manufacture of a medicament, in particular for the manufacture of a medicament for the prevention of, delay of progression of treatment of a disease or condition characterized by the metabolic syndrome.

  本发明涉及一种药物组合物，包括(a)醛固酮合成酶抑制剂或其药学上可接受的盐，和(b)糖皮质激素受体拮抗剂或皮质醇合成抑制剂或皮质醇再合成抑制剂或促肾上腺皮质激素释放激素受体拮抗剂或其组合或在每种情况下其药学上可接受的盐。所述组合物可用于制造药物，特别是用于制造预防、延缓进展或治疗以代谢综合征为特征的疾病或病症的药物。
• Pharmaceutical composition, comprising a steroid-dehydrogenase-reductase inhibitor, and a mineralocorticoid receptor antagonist.
  申请人：OntoChem GmbH

  公开号：EP2243494A1

  公开（公告）日：2010-10-27

  A treatment using a hydroxysteroid dehydrogenase reductase inhibitor combined with a mineralocorticoid receptor antagonist is provided which overcomes the problem that manipulating cortisol levels by a single compound therapy induces other pathologies or side effects, while the original condition that required treatment is ameliorated.

  提供了一种使用羟基类固醇脱氢酶还原酶抑制剂与矿物皮质激素受体拮抗剂相结合的治疗方法，该方法克服了通过单一化合物疗法控制皮质醇水平会诱发其他病症或副作用的问题，而需要治疗的原有病症却得到了改善。
• Methods and compositions for treating alcohol use disorders
  申请人：Sanna Pietro Paolo

  公开号：US10039772B2

  公开（公告）日：2018-08-07

  Disclosed are methods and compositions for treating alcohol dependence by administration to a patient of an inhibitor of 11β-hydroxysteroid dehydrogenases (11β-HSD) to modulate glucocorticoid effects. One such compound is the 11β-HSD inhibitor carbenoxolone (18β-glycyrrhetinic acid 3β-O-hemisuccinate), which has been extensively employed in the clinic for the treatment of gastritis and peptic ulcer. Carbenoxolone is active on both 11β-HSD1 and 2 isoforms. Here, carbenoxolone is surprisingly shown to reduce both baseline and excessive drinking in rats and mice. The carbenoxolone diastereomer 18α-glycyrrhetinic acid 3β-O-hemisuccinate (αCBX), which the applicants discovered to be selective for 11β-HSD2, was also effective in reducing alcohol drinking in mice. Thus, 11β-HSD inhibitors are a new class of candidate alcohol abuse medications and existing 11β-HSD inhibitor drugs may be re-purposed for alcohol abuse treatment.

  本发明公开了通过向患者施用 11β-羟基类固醇脱氢酶（11β-HSD）抑制剂以调节糖皮质激素作用来治疗酒精依赖症的方法和组合物。其中一种化合物是 11β-HSD 抑制剂卡本诺酮（18β-甘草次酸 3β-O-hemisuccinate ），临床上已广泛用于治疗胃炎和消化性溃疡。卡贝诺酮对 11β-HSD1 和 2 同工酶均有活性。令人惊讶的是，羧甲诺龙在大鼠和小鼠体内可减少基线饮酒量和过量饮酒量。申请人发现，羧诺龙的非对映异构体 18α-甘草次酸 3β-O-hemisuccinate (αCBX)对 11β-HSD2 具有选择性，也能有效减少小鼠的饮酒量。因此，11β-HSD 抑制剂是一类新的候选酗酒药物，现有的 11β-HSD 抑制剂药物可重新用于酗酒治疗。
• FXR agonist compositions for combination therapy
  申请人：Intercept Pharmaceuticals, Inc.

  公开号：US10894054B2

  公开（公告）日：2021-01-19

  The present application relates to a pharmaceutical composition comprising a combination of an FXR agonist and at least one additional therapeutic agent that lowers the glucose level in the blood, stimulates insulin secretion, and/or increases insulin sensitivity. The present application relates to use of the pharmaceutical composition for the treatment or prevention of a FXR mediated disease or condition, such as NAFLD and NASH, a disease or condition related to an elevated level of glucose in the blood, decreased secretion of insulin, and/or decreased insulin sensitivity such as hyperglycemia, diabetes, obesity, and insulin resistance, or for lowering the glucose level in the blood, stimulating insulin secretion, and/or increasing insulin sensitivity.

  本申请涉及一种药物组合物，其包含一种FXR激动剂和至少一种额外治疗剂的组合，该治疗剂可降低血液中的葡萄糖水平、刺激胰岛素分泌和/或增加胰岛素敏感性。本申请涉及该药物组合物用于治疗或预防FXR介导的疾病或病症，如非酒精性脂肪肝和NASH，与血液中葡萄糖水平升高、胰岛素分泌减少和/或胰岛素敏感性降低有关的疾病或病症，如高血糖、糖尿病、肥胖和胰岛素抵抗，或用于降低血液中葡萄糖水平、刺激胰岛素分泌和/或增加胰岛素敏感性。