10,10-bis[(pyridazin-4-yl)methyl]-9,10-dihydroanthracen-9-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 10,10-bis[(pyridazin-4-yl)methyl]-9,10-dihydroanthracen-9-one
• 英文别名: 10,10-Bis(pyridazin-4-ylmethyl)anthracen-9-one；10,10-bis(pyridazin-4-ylmethyl)anthracen-9-one
• 化学式: C₂₄H₁₈N₄O
• 分子量: 378.433
• InChiKey: REYRVLDSUZWNSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  68.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  哒嗪-4-甲酸甲酯 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 13.53h， 生成 10,10-bis[(pyridazin-4-yl)methyl]-9,10-dihydroanthracen-9-one
  参考文献：
  名称：

  An anthrone-based Kv7.2/7.3 channel blocker with improved properties for the investigation of psychiatric and neurodegenerative disorders

  摘要：

  A set of novel Kv7.2/7.3 (KCNQ2/3) channel blockers was synthesized to address several liabilities of the known compounds XE991 (metabolic instability and CYP inhibition) and the clinical compound DMP 543 (acid instability, insolubility, and lipophilicity). Using the anthrone scaffold of the prior channel blockers, alternative heteroarylmethyl substituents were installed via enolate alkylation reactions. Incorporation of a pyridazine and a fluorinated pyridine gave an analog (compound 18, JDP-107) with a promising combination of potency (IC50=0.16 mu M in a Kv7.2 thallium flux assay), efficacy in a Kv7.2/7.3 patch clamp assay, and drug-like properties.

  DOI：

  10.1016/j.bmcl.2019.126681

文献信息

• An anthrone-based Kv7.2/7.3 channel blocker with improved properties for the investigation of psychiatric and neurodegenerative disorders
  作者：Jacob D. Porter、Oscar Vivas、C. David Weaver、Abdulmohsen Alsafran、Elliot DiMilo、Leggy A. Arnold、Eamonn J. Dickson、Chris Dockendorff

  DOI：10.1016/j.bmcl.2019.126681

  日期：2019.12

  A set of novel Kv7.2/7.3 (KCNQ2/3) channel blockers was synthesized to address several liabilities of the known compounds XE991 (metabolic instability and CYP inhibition) and the clinical compound DMP 543 (acid instability, insolubility, and lipophilicity). Using the anthrone scaffold of the prior channel blockers, alternative heteroarylmethyl substituents were installed via enolate alkylation reactions. Incorporation of a pyridazine and a fluorinated pyridine gave an analog (compound 18, JDP-107) with a promising combination of potency (IC50=0.16 mu M in a Kv7.2 thallium flux assay), efficacy in a Kv7.2/7.3 patch clamp assay, and drug-like properties.