(R)-2-methyl-1-(2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-2-yl)ethyl)pyrrolidine | 936850-38-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (R)-2-methyl-1-(2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-2-yl)ethyl)pyrrolidine
• CAS: 936850-38-3
• 化学式: C₂₁H₃₀BNO₃
• 分子量: 355.285
• InChiKey: JRTWZHIVROTESD-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.76
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  34.84
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (R)-2-methyl-1-(2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-2-yl)ethyl)pyrrolidine 、 5-溴烟腈 在 bis-triphenylphosphine-palladium(II) chloride sodium carbonate 作用下， 以 水 、 异丙醇 为溶剂， 反应 15.0h， 以70%的产率得到A-698418
  参考文献：
  名称：

  Novel heterocyclic-substituted benzofuran histamine H3 receptor antagonists: In vitro properties, drug-likeness, and behavioral activity

  摘要：

  Three novel heterocyclic benzofurans A-688057 (1), A-687136 (2), and A-698418 (3) were profiled for their in vitro and in vivo properties as a new series of histamine H-3 receptor antagonists. The compounds were all found to have nanomolar potency in vitro at histamine H-3 receptors, and when profiled in vivo for CNS activity, all were found active in an animal behavioral model of attention. The compound with the most benign profile versus CNS side effects was selected for greater scrutiny of its in vitro properties and overall drug-likeness. This compound, A-688057, in addition to its potent and robust efficacy in two rodent behavioral models at blood levels ranging 0.2-19 nM, possessed other favorable features, including high selectivity for H-3 receptors (H-3, K-i = 13 nM) versus off-target receptors and channels (including the hERG K+ channel, K-i > 9000 nM), low molecular weight (295), high solubility, moderate lipophilicity (logD(pH7.4) = 2.05), and good CNS penetration (blood/brain 3.4x). In vitro toxicological tests indicated low potential for phospholipidosis, genotoxicity, and CYP450 inhibition. Even though pharmacokinetic testing uncovered only moderate to poor oral bioavailability in rat (26%), dog (30%), and monkey (8%), and only moderate blood half-lives after i.v. administration (t(1/2) in rat of 2.9 h, 1.7 h in dog, 1.8 h in monkey), suggesting poor human pharmacokinetics, the data overall indicated that A-688057 has an excellent profile for use as a pharmacological tool compound. (c) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2007.02.010
• 作为产物：
  描述：

  联硼酸频那醇酯 、 1-[2-(5-bromo-1-benzofuran-2-yl)ethyl]-2(R)-methylpyrrolidine 在 1,1'-bis(diphenylphosphino)ferrocene palladium dichloride potassium acetate 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 21.0h， 以3.5 g的产率得到(R)-2-methyl-1-(2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-2-yl)ethyl)pyrrolidine
  参考文献：
  名称：

  Novel heterocyclic-substituted benzofuran histamine H3 receptor antagonists: In vitro properties, drug-likeness, and behavioral activity

  摘要：

  Three novel heterocyclic benzofurans A-688057 (1), A-687136 (2), and A-698418 (3) were profiled for their in vitro and in vivo properties as a new series of histamine H-3 receptor antagonists. The compounds were all found to have nanomolar potency in vitro at histamine H-3 receptors, and when profiled in vivo for CNS activity, all were found active in an animal behavioral model of attention. The compound with the most benign profile versus CNS side effects was selected for greater scrutiny of its in vitro properties and overall drug-likeness. This compound, A-688057, in addition to its potent and robust efficacy in two rodent behavioral models at blood levels ranging 0.2-19 nM, possessed other favorable features, including high selectivity for H-3 receptors (H-3, K-i = 13 nM) versus off-target receptors and channels (including the hERG K+ channel, K-i > 9000 nM), low molecular weight (295), high solubility, moderate lipophilicity (logD(pH7.4) = 2.05), and good CNS penetration (blood/brain 3.4x). In vitro toxicological tests indicated low potential for phospholipidosis, genotoxicity, and CYP450 inhibition. Even though pharmacokinetic testing uncovered only moderate to poor oral bioavailability in rat (26%), dog (30%), and monkey (8%), and only moderate blood half-lives after i.v. administration (t(1/2) in rat of 2.9 h, 1.7 h in dog, 1.8 h in monkey), suggesting poor human pharmacokinetics, the data overall indicated that A-688057 has an excellent profile for use as a pharmacological tool compound. (c) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2007.02.010