2-methoxy-5-(1-methyl-1H-imidazol-2-yl)benzenemethanol | 202822-81-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-methoxy-5-(1-methyl-1H-imidazol-2-yl)benzenemethanol
• 英文别名: [2-Methoxy-5-(1-methylimidazol-2-yl)phenyl]methanol
• CAS: 202822-81-9
• 化学式: C₁₂H₁₄N₂O₂
• 分子量: 218.255
• InChiKey: VXPNYPMJMAFJIM-UHFFFAOYSA-N

物化性质

• 熔点：
  116.5-118 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  422.6±55.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  47.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methoxy-5-(1-methyl-1H-imidazol-2-yl)benzenemethanol 在 三溴化硼 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 42.0h， 生成 3-[[5-(1-methyl-1H-imidazol-2-yl)-2-hydroxyphenyl]methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-(3H)-one
  参考文献：
  名称：

  3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-oxadiazol-2(3H)-one, BMS-191011:  Opener of Large-Conductance Ca²⁺-Activated Potassium (Maxi-K) Channels, Identification, Solubility, and SAR

  摘要：

  Compound 8a (BMS-191011), an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. However, 8a suffered from poor aqueous solubility, which complicated elucidation of SAR during in vitro evaluation. The activity of 8a in in vivo stroke models and studies directed toward improving its solubility are reported herein. Enhanced solubility was achieved by appending heterocycles to the 8a scaffold, and a notable observation was made that inclusion of a simple amino group (anilines 8k and 8l) yielded excellent in vitro maxi-K ion channel opening activity and enhanced brain-to-plasma partitioning compared to the appended heterocycles.

  DOI：

  10.1021/jm061006n
• 作为产物：
  描述：

  5-溴-2-甲氧基苯甲醇 在 咪唑 、 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 2-methoxy-5-(1-methyl-1H-imidazol-2-yl)benzenemethanol
  参考文献：
  名称：

  3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-oxadiazol-2(3H)-one, BMS-191011:  Opener of Large-Conductance Ca²⁺-Activated Potassium (Maxi-K) Channels, Identification, Solubility, and SAR

  摘要：

  Compound 8a (BMS-191011), an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. However, 8a suffered from poor aqueous solubility, which complicated elucidation of SAR during in vitro evaluation. The activity of 8a in in vivo stroke models and studies directed toward improving its solubility are reported herein. Enhanced solubility was achieved by appending heterocycles to the 8a scaffold, and a notable observation was made that inclusion of a simple amino group (anilines 8k and 8l) yielded excellent in vitro maxi-K ion channel opening activity and enhanced brain-to-plasma partitioning compared to the appended heterocycles.

  DOI：

  10.1021/jm061006n

文献信息

• DIPHENYL HETEROCYCLES AS POTASSIUM CHANNEL MODULATORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP0915856A1

  公开（公告）日：1999-05-19
• EP0915856A4
  申请人：——

  公开号：EP0915856A4

  公开（公告）日：2006-04-12
• US5869509A
  申请人：——

  公开号：US5869509A

  公开（公告）日：1999-02-09
• US6077861A
  申请人：——

  公开号：US6077861A

  公开（公告）日：2000-06-20
• US6271249B1
  申请人：——

  公开号：US6271249B1

  公开（公告）日：2001-08-07