7-[(3-fluorobenzyl)oxy]-4-[(isopropylamino)methyl]-2H-chromen-2-one methanesulfonate | 1193004-82-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 7-[(3-fluorobenzyl)oxy]-4-[(isopropylamino)methyl]-2H-chromen-2-one methanesulfonate
• 英文别名: 7-[(3-Fluorophenyl)methoxy]-4-[(propan-2-ylamino)methyl]chromen-2-one;methanesulfonic acid
• CAS: 1193004-82-8
• 化学式: CH₄O₃S*C₂₀H₂₀FNO₃
• 分子量: 437.489
• InChiKey: SDHGGDOTYINHTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  7-[(3-fluorobenzyl)oxy]-4-[(isopropylamino)methyl]-2H-chromen-2-one 、 甲烷磺酸 以 四氢呋喃 为溶剂， 生成 7-[(3-fluorobenzyl)oxy]-4-[(isopropylamino)methyl]-2H-chromen-2-one methanesulfonate
  参考文献：
  名称：

  Discovery of a Novel Class of Potent Coumarin Monoamine Oxidase B Inhibitors: Development and Biopharmacological Profiling of 7-[(3-Chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one Methanesulfonate (NW-1772) as a Highly Potent, Selective, Reversible, and Orally Active Monoamine Oxidase B Inhibitor

  摘要：

  In an effort to discover novel selective monoamine oxidase (MAO) B inhibitors with favorable physicochemical and pharmacokinetic profiles, 7-[m-halogeno)benzyloxy]coumarins bearing properly selected polar substituents at position 4 were designed, synthesized, and evaluated as MAO inhibitors. Several compounds with MAO-B inhibitory activity in the nanomolar range and excellent MAO-B selectivity (selectivity index SI > 400) were identified. Structure-affinity relationships and docking simulations provided valuable insights into the enzyme-inhibitor binding interactions at position 4, which has been poorly explored. Furthermore, computational and experimental studies led to the identification and biopharmacological characterization of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate 22b (NW-1772) as an in vitro and in vivo potent and selective MAO-B inhibitor, with rapid blood-brain barrier penetration, short-acting and reversible inhibitory activity, slight inhibition of selected cytochrome P450s, and low in vitro toxicity. On the basis of this preliminary preclinical profile, inhibitor 22b might be viewed as a promising clinical candidate for the treatment of neurodegenerative diseases.

  DOI：

  10.1021/jm9010127