4-F¹⁹-salicylihalamide B | 1107631-40-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: 4-F¹⁹-salicylihalamide B
• 英文别名: 4-19F-Salicylihalamide B；(2Z,4Z)-N-[(Z)-3-[(4S,6R,7S,9E)-15-fluoro-6,16-dihydroxy-7-methyl-2-oxo-3-oxabicyclo[10.4.0]hexadeca-1(12),9,13,15-tetraen-4-yl]prop-1-enyl]hepta-2,4-dienamide
• CAS: 1107631-40-2
• 化学式: C₂₆H₃₂FNO₅
• 分子量: 457.542
• InChiKey: UZYHYMLJNHZVAQ-DGNSGBGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  、 (2Z,4Z)-hepta-2,4-dienoic acid amide 在 rubidium carbonate 、 2,2'-联吡啶 、 噻吩-2-甲酸亚铜(I) 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 1.0h， 以15%的产率得到4-F¹⁹-salicylihalamide A
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Fluorinated Analogues of Salicylihalamide

  摘要：

  Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent cytotoxicity against human tumor cell lines. SA is a selective inhibitor of mammalian vacuolar type H+-ATPase (V-ATPase), and is distinct from previously known V-ATPase inhibitors such as bafilomycins and concanamycins that do not discriminate between mammalian and nonmammalian V-ATPases. Because of its potent antitumor activity and structural simplicity, SA is a promising candidate for an anticancer drug. Although a number of structure-activity relation studies using synthetic analogues have been reported, no fluorinated derivative of SA has been evaluated even though selective addition of a fluorine atom into a therapeutic small molecule candidate often enhances pharmacokinetic and physicochemical properties. We designed and synthesized fluorinated analogues of SA and evaluated their V-ATPase inhibitory activities. Compared to the natural product, the synthetic analogues were potent V-ATPase inhibitors, suggesting that these analogues are potential drug candidates and potential molecular probes for mode-of-action studies using fluorine-based analytical methods such as F-19-NMR spectroscopy.

  DOI：

  10.1021/jm801265e

文献信息

• Design, Synthesis, and Biological Evaluation of Fluorinated Analogues of Salicylihalamide
  作者：Yoshinori Sugimoto、Keiichi Konoki、Michio Murata、Masafumi Matsushita、Hiroshi Kanazawa、Tohru Oishi

  DOI：10.1021/jm801265e

  日期：2009.2.12

  Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent cytotoxicity against human tumor cell lines. SA is a selective inhibitor of mammalian vacuolar type H+-ATPase (V-ATPase), and is distinct from previously known V-ATPase inhibitors such as bafilomycins and concanamycins that do not discriminate between mammalian and nonmammalian V-ATPases. Because of its potent antitumor activity and structural simplicity, SA is a promising candidate for an anticancer drug. Although a number of structure-activity relation studies using synthetic analogues have been reported, no fluorinated derivative of SA has been evaluated even though selective addition of a fluorine atom into a therapeutic small molecule candidate often enhances pharmacokinetic and physicochemical properties. We designed and synthesized fluorinated analogues of SA and evaluated their V-ATPase inhibitory activities. Compared to the natural product, the synthetic analogues were potent V-ATPase inhibitors, suggesting that these analogues are potential drug candidates and potential molecular probes for mode-of-action studies using fluorine-based analytical methods such as F-19-NMR spectroscopy.