1-(4-phenoxybutoxy)naphthalene | 1158849-37-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(4-phenoxybutoxy)naphthalene
• CAS: 1158849-37-6
• 化学式: C₂₀H₂₀O₂
• 分子量: 292.378
• InChiKey: BNQMOAFESUFQJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  萘酚 、 4-苯氧基丁基溴 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以9%的产率得到1-(4-phenoxybutoxy)naphthalene
  参考文献：
  名称：

  4-Phenoxybutoxy-substituted heterocycles – A structure–activity relationship study of blockers of the lymphocyte potassium channel Kv1.3

  摘要：

  The voltage-gated potassium channel Kv1.3 constitutes an attractive pharmacological target for the treatment of effector memory T cell-mediated autoimmune diseases such as multiple sclerosis and psoriasis. Using 5-methoxypsoralen (5-MOP, 1), a compound isolated from Ruta graveolens, as a template we previously synthesized 5-(4-phenoxybutoxy)psoralen (PAP-1, 2) which inhibits Kv1.3 with an IC(50) of 2 nM. Since PAP-1 is more than 1000-fold more potent than 5-MOP, we here investigated whether attaching a 4-phenoxybutoxy side chain to other heterocyclic systems would also produce potent Kv1.3 blockers. While 4-phenoxybutoxy-substituted quinolines, quinazolines and phenanthrenes were inactive, 4-phenoxybutoxy-substituted quinolinones, furoquinolines, coumarins or furochromones inhibited Kv1.3 with IC(50)s of 150 nM to 10 mu M in whole-cell patch-clamp experiments. Our most potent new compound is 4-(4-phenoxybutoxy)-7H-furo[3,2-g]chromene-7-thione (73, IC(50) 17 nM), in which the carbonyl oxygen of PAP-1 is replaced by sulfur. Taken together, our results demonstrate that the psoralen system is a crucial part of the pharmacophore of phenoxyalkoxypsoralen-type Kv1.3 blockers. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.10.033

文献信息

• 4-Phenoxybutoxy-substituted heterocycles – A structure–activity relationship study of blockers of the lymphocyte potassium channel Kv1.3
  作者：Silke B. Bodendiek、Cédrick Mahieux、Wolfram Hänsel、Heike Wulff

  DOI：10.1016/j.ejmech.2008.10.033

  日期：2009.5

  The voltage-gated potassium channel Kv1.3 constitutes an attractive pharmacological target for the treatment of effector memory T cell-mediated autoimmune diseases such as multiple sclerosis and psoriasis. Using 5-methoxypsoralen (5-MOP, 1), a compound isolated from Ruta graveolens, as a template we previously synthesized 5-(4-phenoxybutoxy)psoralen (PAP-1, 2) which inhibits Kv1.3 with an IC(50) of 2 nM. Since PAP-1 is more than 1000-fold more potent than 5-MOP, we here investigated whether attaching a 4-phenoxybutoxy side chain to other heterocyclic systems would also produce potent Kv1.3 blockers. While 4-phenoxybutoxy-substituted quinolines, quinazolines and phenanthrenes were inactive, 4-phenoxybutoxy-substituted quinolinones, furoquinolines, coumarins or furochromones inhibited Kv1.3 with IC(50)s of 150 nM to 10 mu M in whole-cell patch-clamp experiments. Our most potent new compound is 4-(4-phenoxybutoxy)-7H-furo[3,2-g]chromene-7-thione (73, IC(50) 17 nM), in which the carbonyl oxygen of PAP-1 is replaced by sulfur. Taken together, our results demonstrate that the psoralen system is a crucial part of the pharmacophore of phenoxyalkoxypsoralen-type Kv1.3 blockers. (C) 2008 Elsevier Masson SAS. All rights reserved.