8-(2-bromoethoxy)-6-fluorochroman | 188826-33-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 8-(2-bromoethoxy)-6-fluorochroman
• 英文别名: 8-(2-bromoethoxy)-6-fluoro-3,4-dihydro-2H-chromene
• CAS: 188826-33-7
• 化学式: C₁₁H₁₂BrFO₂
• 分子量: 275.117
• InChiKey: OMGHXZXSKVFMLO-UHFFFAOYSA-N

物化性质

• 沸点：
  333.0±42.0 °C(Predicted)
• 密度：
  1.485±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-(2-bromoethoxy)-6-fluorochroman 在 palladium on activated charcoal 甲酸 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 4.0h， 生成 2-(6-fluorochroman-8-yloxy)ethylamine
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Novel 6-Fluorochroman Derivatives as Potential 5-HT_1A Receptor Antagonists

  摘要：

  A series of novel 6-fluorochroman derivatives was prepared and evaluated as antagonists for the 5-HT1A receptor. N-2- [[(6-Fluorochroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamine (3; J. Med. Chem. 1997, 40, 1252-1257) was chosen as a lead, and structural modifications were done on the aliphatic portion of the chroman ring, the tether linking the middle amine and the terminal aromatic ring, the aromatic ring, and lastly the amine. Radioligand binding assays proved that the majority of the novel compounds behaved as good to excellent ligands at the 5-HT1A receptor, some of which were selective with respect to alpha(1)-adrenergic and D-2-dopaminergic receptors. The antagonist activity of the compounds was assessed in the forskolin-stimulated adenylate cyclase assays in CHO cells expressing the human 5-HT1A receptors. Among the modifications attempted, introduction of an oxo or an optically active hydroxy moiety at the chroman C-4 position was effective in ameliorating the receptor selectivity. Six analogues were selected through the in vitro screeds and further evaluated for their in vivo activities. A 4-oxochroman derivative (31n), having a terminal 1,3-benzodioxole ring, demonstrated antagonist activities toward 8-OH-DPAT-induced behavioral and electrophysiological responses in rats.

  DOI：

  10.1021/jm9707840
• 作为产物：
  描述：

  6-氟苯并二氢吡喃 在 sodium hydroxide 、 三氯化铝 、 四丁基硫酸氢铵 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 18.0h， 生成 8-(2-bromoethoxy)-6-fluorochroman
  参考文献：
  名称：

  N- [2-[（取代的苯并吡喃-8-基）氧基]乙基] -4-（4-甲氧基苯基）丁胺：在人类5-HT1A受体上的合成及其拮抗作用。

  摘要：

  制备了一系列的N- [2-[（取代的苯并吡喃-8-基）氧基]乙基] -4-（4-甲氧基苯基）丁胺，并检查了它们的5-HT1A受体拮抗剂活性。由相应的8-羟基苯并二氢吡喃中间体制备母体化合物3a和在苯并吡喃环上带有五种取代基的七个类似物。放射性配体结合试验证明化合物3a-h对大鼠海马5-HT1A受体具有高亲和力，对肾上腺素α1和多巴胺D2受体具有不同的选择性。在用表达人5-HT1A受体的CHO细胞进行的福斯科林刺激的腺苷酸环化酶测定中评估了它们的拮抗作用。在该系列中，C6-氟类似物3c对5-HT1A受体显示出极强的亲和力（Ki = 0.22 nM）和拮抗作用（EC50 = 13 nM）。

  DOI：

  10.1021/jm960760d

文献信息

• Synthesis and Pharmacological Characterization of Novel 6-Fluorochroman Derivatives as Potential 5-HT_1A Receptor Antagonists
  作者：Tomoyuki Yasunaga、Takenori Kimura、Ryo Naito、Toru Kontani、Fumikazu Wanibuchi、Hiroshi Yamashita、Tamako Nomura、Shin-ichi Tsukamoto、Tokio Yamaguchi、Toshiyasu Mase

  DOI：10.1021/jm9707840

  日期：1998.7.1

  A series of novel 6-fluorochroman derivatives was prepared and evaluated as antagonists for the 5-HT1A receptor. N-2- [[(6-Fluorochroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamine (3; J. Med. Chem. 1997, 40, 1252-1257) was chosen as a lead, and structural modifications were done on the aliphatic portion of the chroman ring, the tether linking the middle amine and the terminal aromatic ring, the aromatic ring, and lastly the amine. Radioligand binding assays proved that the majority of the novel compounds behaved as good to excellent ligands at the 5-HT1A receptor, some of which were selective with respect to alpha(1)-adrenergic and D-2-dopaminergic receptors. The antagonist activity of the compounds was assessed in the forskolin-stimulated adenylate cyclase assays in CHO cells expressing the human 5-HT1A receptors. Among the modifications attempted, introduction of an oxo or an optically active hydroxy moiety at the chroman C-4 position was effective in ameliorating the receptor selectivity. Six analogues were selected through the in vitro screeds and further evaluated for their in vivo activities. A 4-oxochroman derivative (31n), having a terminal 1,3-benzodioxole ring, demonstrated antagonist activities toward 8-OH-DPAT-induced behavioral and electrophysiological responses in rats.
• <i>N</i>-[2-[(Substituted chroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamines:  Synthesis and Wide Range of Antagonism at the Human 5-HT_1A Receptor
  作者：Tomoyuki Yasunaga、Ryo Naito、Toru Kontani、Shin-ichi Tsukamoto、Tamako Nomura、Tokio Yamaguchi、Toshiyasu Mase

  DOI：10.1021/jm960760d

  日期：1997.4.1

  A series of N-[2-[(substituted chroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamines was prepared and examined for their 5-HT1A receptor antagonist activity. The parent compound 3a and seven analogs bearing five kinds of substituents on the chroman ring were prepared from the corresponding 8-hydroxychroman intermediates. Radioligand binding assays proved the compounds 3a-h to have high affinity for

  制备了一系列的N- [2-[（取代的苯并吡喃-8-基）氧基]乙基] -4-（4-甲氧基苯基）丁胺，并检查了它们的5-HT1A受体拮抗剂活性。由相应的8-羟基苯并二氢吡喃中间体制备母体化合物3a和在苯并吡喃环上带有五种取代基的七个类似物。放射性配体结合试验证明化合物3a-h对大鼠海马5-HT1A受体具有高亲和力，对肾上腺素α1和多巴胺D2受体具有不同的选择性。在用表达人5-HT1A受体的CHO细胞进行的福斯科林刺激的腺苷酸环化酶测定中评估了它们的拮抗作用。在该系列中，C6-氟类似物3c对5-HT1A受体显示出极强的亲和力（Ki = 0.22 nM）和拮抗作用（EC50 = 13 nM）。