2-methyl-6,7-methylenedioxy-5-methoxy-4H-[1]-benzopyran-4-one | 914222-21-2

• 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: 2-methyl-6,7-methylenedioxy-5-methoxy-4H-[1]-benzopyran-4-one
• 英文别名: 9-Methoxy-6-methyl-[1,3]dioxolo[4,5；9-methoxy-6-methyl-[1,3]dioxolo[4,5-g]chromen-8-one
• CAS: 914222-21-2
• 化学式: C₁₂H₁₀O₅
• 分子量: 234.208
• InChiKey: BTZCNQUNVGKAPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methyl-6,7-methylenedioxy-5-methoxy-4H-[1]-benzopyran-4-one 在 三溴化硼 、 水 作用下， 以 二氯甲烷 为溶剂， 以85%的产率得到5-hydroxy-2-methyl-6,7-methylendioxy-4H-[1]benzopyran-4-one
  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
• 作为产物：
  描述：

  6,7-dihydroxy-5-methoxy-2-methyl-4H-[1]benzopyran-4-one 、 二溴甲烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以35.4%的产率得到2-methyl-6,7-methylenedioxy-5-methoxy-4H-[1]-benzopyran-4-one
  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.