4-[3-(benzylaminomethyl)-4-methoxyphenyl]-3-bromo-5-hydroxy-5H-furan-2-one | 1237737-69-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[3-(benzylaminomethyl)-4-methoxyphenyl]-3-bromo-5-hydroxy-5H-furan-2-one
• 英文别名: 3-[3-[(benzylamino)methyl]-4-methoxyphenyl]-4-bromo-2-hydroxy-2H-furan-5-one
• CAS: 1237737-69-7
• 化学式: C₁₉H₁₈BrNO₄
• 分子量: 404.26
• InChiKey: HBYVBYFBIQRICZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苄胺 在 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 三异丙基硅烷 、 四丁基溴化铵 、 水 、 sodium cyanoborohydride 、 三乙胺 、 cesium fluoride 、 三氟乙酸 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 120.0 ℃ 、1.72 MPa 条件下， 反应 5.5h， 生成 4-[3-(benzylaminomethyl)-4-methoxyphenyl]-3-bromo-5-hydroxy-5H-furan-2-one
  参考文献：
  名称：

  Toward the Discovery of New Agents Able to Inhibit the Expression of Microsomal Prostaglandin E Synthase-1 Enzyme as Promising Tools in Drug Development

  摘要：

  In our recent studies, we focused our attention on the synthesis of several γ‐hydroxybutenolides designed on the basis of petrosaspongiolide M 1 (PM) structure that has been recognized to potently inhibit the inflammatory process through the selective PLA2 enzyme inhibition. By means of a combination of computational methods and efficient synthetic strategies, we generated small collections of PM modified analogs to identify new potent PLA2 inhibitors, suitable for clinical development. In the course of the biological screening of our compounds, we discovered a potent and selective inhibitor of mPGES‐1 expression, the benzothiophene γ‐hydroxybutenolide 2, which so far represents the only product, together with resveratrol, able to reduce PGE2 production through the selective downregulation of mPGES‐1 enzyme. In consideration that microsomal prostaglandin E synthase 1 (mPGES‐1) is one of the most strategic target involved both in inflammation and in carcinogenesis processes, we decided to explore the biological effects of some structural changes of the γ‐hydroxybutenolide 2, hoping to improve its biological profile. This optimization process led to the identification of three strictly correlated compounds 14g, 16g, and 18 with higher inhibitory potency on PGE2 production on mouse macrophage cell line RAW264.7 through the selective modulation of mPGES‐1 enzyme expression.

  DOI：

  10.1111/j.1747-0285.2010.00984.x