3-fluoro-3-(3-methyl-pyridin-2-yl)-8-aza-bicyclo[3.2.1]octane | 1346014-74-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 3-fluoro-3-(3-methyl-pyridin-2-yl)-8-aza-bicyclo[3.2.1]octane
• 英文别名: 3-fluoro-3-(3-methylpyridin-2-yl)-8-azabicyclo[3.2.1]octane
• CAS: 1346014-74-1
• 化学式: C₁₃H₁₇FN₂
• 分子量: 220.29
• InChiKey: WZCDWYILXHBQKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(1H-pyrazol-4-yl)-thiophene-3-carboxylic acid 、 3-fluoro-3-(3-methyl-pyridin-2-yl)-8-aza-bicyclo[3.2.1]octane 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 [3-fluoro-3-(3-methyl-pyridin-2-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone 、 [3-fluoro-3-(3-methyl-pyridin-2-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone
  参考文献：
  名称：

  [EN] 3, 3 -DISUBSTITUTED- ( 8 - AZA - BICYCLO [3.2.1] OCT- 8 - YL) -[5- (1H - PYRAZOL - 4 -YL) -THIOPHEN-3 -YL] METHANONES AS INHIBITORS OF 11 (BETA) -HSD1
  [FR] (8-AZA-BICYCLO[3.2.1]OCT-8-YL)-[5-(1H-PYRAZOL-4-YL]-MÉTHANONES 3,3-DISUBSTITUÉES EN TANT QU'INHIBITEURS DE 11-(BÊTA)-HSD1

  摘要：

  本发明通常涉及治疗化合物领域。更具体地，本发明涉及某些3,3-二取代-(8-aza-双环[3.2.1]辛-8-基)[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮，3,3-二取代-(6-aza-双环[3.1.1]庚-6-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮和4,4-二取代哌啶-1-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮的化合物，其具有以下式（I）的结构，其在某种程度上抑制11β-羟基甾醇脱氢酶1（11β-HSD1）。本发明还涉及包含这些化合物的药物组合物，以及在体内外使用这些化合物和组合物抑制11β-羟基甾醇脱氢酶1；治疗通过抑制11β-羟基甾醇脱氢酶1而改善的疾病；治疗代谢综合征，包括2型糖尿病和肥胖等疾病，以及相关疾病，包括胰岛素抵抗、高血压、脂质紊乱和心血管疾病，如缺血性（冠状）心脏病；治疗中枢神经系统疾病，如轻度认知障碍和早期痴呆，包括阿尔茨海默病等。

  公开号：

  WO2011135276A1

文献信息

• 3,3-DISUBSTITUTED-(8-AZA-BICYCLO[3.2.1]OCT-8-YL)-[5-(1H-PYRAZOL-4-YL)-THIOPHEN-3-YL]-METHANONES AS INHIBITORS OF 11 (BETA)-HSD1
  申请人：Webster Scott Peter

  公开号：US20130123268A1

  公开（公告）日：2013-05-16

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3,3-disubstituted-(8-aza-bicyclo[3.2.1]oct-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, 3,3-disubstituted-(6-aza-bicyclo[3.1.1]hept-6-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, and 4,4-disubstituted piperidin-1-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds of the following formula that, inter alia, inhibit 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.

  本发明涉及治疗化合物领域。更具体地，本发明涉及以下化合物的某些3,3-二取代-(8-氮杂双环[3.2.1]辛-8-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮，3,3-二取代-(6-氮杂双环[3.1.1]庚-6-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮和4,4-二取代哌啶-1-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮化合物，其中包括抑制11β-羟化甾酮脱氢酶1型(11β-HSD1)的作用。本发明还涉及包含这些化合物的制药组合物，以及使用这些化合物和组合物在体内外抑制11β-羟化甾酮脱氢酶1型；治疗通过抑制11β-羟化甾酮脱氢酶1型而改善的疾病；治疗代谢综合征，包括2型糖尿病和肥胖症等疾病，以及相关疾病，包括胰岛素抵抗、高血压、脂质代谢紊乱和缺血(冠状动脉)性心脏病；治疗CNS疾病，如轻度认知障碍和早期痴呆，包括阿尔茨海默病等。
• 3,3-disubstituted-(8-aza-bicyclo[3.2.1]oct-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanones as inhibitors of 11 (β)-HSD1
  申请人：Webster Scott Peter

  公开号：US09365564B2

  公开（公告）日：2016-06-14

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3,3-disubstituted-(8-aza-bicyclo[3.2.1]oct-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, 3,3-disubstituted-(6-aza-bicyclo[3.1.1]hept-6-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, and 4,4-disubstituted piperidin-1-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds of the following formula that, inter alia, inhibit 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.

  本发明一般涉及治疗化合物领域。更具体地，本发明涉及某些3,3-二取代-(8-氮杂双环[3.2.1]辛-8-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮、3,3-二取代-(6-氮杂双环[3.1.1]庚-6-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮和4,4-二取代哌啶-1-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮化合物，其化学式如下，可抑制11β-羟基类固醇脱氢酶1型（11β-HSD1）等。本发明还涉及包括这些化合物的制药组合物以及使用这些化合物和组合物在体外和体内抑制11β-羟基类固醇脱氢酶1型；治疗由抑制11β-羟基类固醇脱氢酶1型改善的疾病；治疗代谢综合征，包括2型糖尿病和肥胖症等疾病，并伴随有胰岛素抵抗、高血压、脂质紊乱和缺血性（冠状动脉）心脏病等相关疾病；治疗中枢神经系统疾病，如轻度认知障碍和早期痴呆，包括阿尔茨海默病等等。
• 3, 3 -DISUBSTITUTED- ( 8 - AZA - BICYCLO [3.2.1]OCT- 8 - YL) -[5- (1H - PYRAZOL - 4 -YL) -THIOPHEN-3 -YL]METHANONES AS INHIBITORS OF 11 (BETA) -HSD1
  申请人：THE UNIVERSITY OF EDINBURGH

  公开号：EP2563780A1

  公开（公告）日：2013-03-06
• 3,3-DISUBSTITUTED-(8-AZA-BICYCLO[3.2.1]OCT-8-YL)-[5-(1H-PYRAZOL-4-YL)-THIOPHEN-3-YL]-METHANONES AS INHIBITORS OF 11(BETA)-HSD1
  申请人：THE UNIVERSITY OF EDINBURGH

  公开号：EP2563780B1

  公开（公告）日：2015-05-06
• US9365564B2
  申请人：——

  公开号：US9365564B2

  公开（公告）日：2016-06-14