5-(4-{1-methyl-5-[2-(trifluoromethyl)phenyl]-1-H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)pentan-2-ol | 719272-72-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(4-{1-methyl-5-[2-(trifluoromethyl)phenyl]-1-H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)pentan-2-ol
• 英文别名: 5-(4-(4-methyl-5-(2-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-3-yl)bicyclo[2.2.2]octan-1-yl)pentan-2-ol；5-[4-[4-methyl-5-[2-(trifluoromethyl)phenyl]-1,2,4-triazol-3-yl]-1-bicyclo[2.2.2]octanyl]pentan-2-ol
• CAS: 719272-72-7
• 化学式: C₂₃H₃₀F₃N₃O
• 分子量: 421.506
• InChiKey: LWSUXLRGYIUHPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  50.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(4-{1-methyl-5-[2-(trifluoromethyl)phenyl]-1-H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)pentan-2-ol 在 二乙胺基三氟化硫 作用下， 生成 C₂₃H₂₉F₄N₃
  参考文献：
  名称：

  Bicyclo[2.2.2]octyltriazole inhibitors of 11β-hydoxysteroid dehydrogenase type 1. Pharmacological agents for the treatment of metabolic syndrome

  摘要：

  Following the discovery of a metabolic 'soft-spot' on a bicyclo[2.2.2]octyltriazole lead, an extensive effort was undertaken to block the oxidative metabolism and improve PK of this potent HSD1 lead. In this communication, SAR survey focusing on various alkyl chain replacements will be detailed. This effort culminated in the discovery of a potent ethyl sulfone inhibitor with an improved PK profile across species and improved physical properties. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.018
• 作为产物：
  描述：

  4-甲酰基双环并[2.2.2]辛烷-1-甲酸甲酯 在 palladium 10% on activated carbon 氢氧化钾 、 sodium tetrahydroborate 、 水 、 氢气 、 双(三甲基硅烷基)氨基钾 、 2-氯-1,3-二甲基氯化咪唑啉 、 对甲苯磺酸 、 三乙胺 、 甲胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 78.5h， 生成 5-(4-{1-methyl-5-[2-(trifluoromethyl)phenyl]-1-H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)pentan-2-ol
  参考文献：
  名称：

  Triazole derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1

  摘要：

  三唑衍生物的结构式I是对11β-羟基类固醇脱氢酶-1的选择性抑制剂。这些化合物可用于治疗糖尿病，如非胰岛素依赖型糖尿病（NIDDM）、高血糖、肥胖、胰岛素抵抗、血脂异常、高脂血症、高血压、代谢综合征以及与非胰岛素依赖型糖尿病相关的其他症状。

  公开号：

  US20040133011A1

文献信息

• TRIAZOLE DERIVATIVES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE-1
  申请人：Waddell Sherman T.

  公开号：US20090181994A1

  公开（公告）日：2009-07-16

  Triazole derivatives of structural formula I are selective inhibitors of the 11β-hydroxysteroid dehydrogenase-1. The compounds are useful for the treatment of diabetes, such as noninsulin-dependent diabetes (NIDDM), hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, Metabolic Syndrome, and other symptoms associated with NIDDM.

  结构式I的三唑衍生物是11β-羟类固醇脱氢酶-1的选择性抑制剂。这些化合物可用于治疗糖尿病，如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，代谢综合症以及与NIDDM相关的其他症状。
• US7504402B2
  申请人：——

  公开号：US7504402B2

  公开（公告）日：2009-03-17
• Triazole derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1
  申请人：——

  公开号：US20040133011A1

  公开（公告）日：2004-07-08

  Triazole derivatives of structural formula I are selective inhibitors of the 11&bgr;-hydroxysteroid dehydrogenase-1. The compounds are useful for the treatment of diabetes, such as noninsulin-dependent diabetes (NIDDM), hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, Metabolic Syndrome, and other symptoms associated with NIDDM.

  三唑衍生物的结构式I是对11β-羟基类固醇脱氢酶-1的选择性抑制剂。这些化合物可用于治疗糖尿病，如非胰岛素依赖型糖尿病（NIDDM）、高血糖、肥胖、胰岛素抵抗、血脂异常、高脂血症、高血压、代谢综合征以及与非胰岛素依赖型糖尿病相关的其他症状。
• Bicyclo[2.2.2]octyltriazole inhibitors of 11β-hydoxysteroid dehydrogenase type 1. Pharmacological agents for the treatment of metabolic syndrome
  作者：Milana Maletic、Aaron Leeman、Michael Szymonifka、Steven S. Mundt、Hratch J. Zokian、Kashmira Shah、Jasminka Dragovic、Kathy Lyons、Rolf Thieringer、Anne H. Vosatka、James Balkovec、Sherman T. Waddell

  DOI：10.1016/j.bmcl.2011.01.018

  日期：2011.4

  Following the discovery of a metabolic 'soft-spot' on a bicyclo[2.2.2]octyltriazole lead, an extensive effort was undertaken to block the oxidative metabolism and improve PK of this potent HSD1 lead. In this communication, SAR survey focusing on various alkyl chain replacements will be detailed. This effort culminated in the discovery of a potent ethyl sulfone inhibitor with an improved PK profile across species and improved physical properties. (C) 2011 Elsevier Ltd. All rights reserved.