4-hydroxy-7,8-dimethoxyfuro[2,3-b]quinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-hydroxy-7,8-dimethoxyfuro[2,3-b]quinoline
• 英文别名: 4-hydroxy-7,8-dimethoxyfuranquinoline；7,8-dimethoxy-9H-furo[2,3-b]quinolin-4-one；norskimmianine；7,8-dimethoxy-9H-furo[2,3-b]quinolin-4-one
• 化学式: C₁₃H₁₁NO₄
• 分子量: 245.235
• InChiKey: PREIMPRRBOZNAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  60.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-苯氧基丁基溴 、 4-hydroxy-7,8-dimethoxyfuro[2,3-b]quinoline 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以11%的产率得到7,8-dimethoxy-4-(4-phenoxybutoxy)furo[2,3-b]quinoline
  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：

  4,7,8-三甲氧基呋喃并[2,3-B]喹啉 在 盐酸 、 水 、 sodium hydroxide 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 10.0h， 以70%的产率得到4-hydroxy-7,8-dimethoxyfuro[2,3-b]quinoline
  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

• Alkaloids of the Australian Rutaceae: Acronychia baueri Schott. IV. Alkaloids present in the leaves
  作者：JA Lamberton、JR Price

  DOI：10.1071/ch9530066

  日期：——

  The leaves of Acronychia baueri Schott. contain the acridine alkaloids melicopine, melicopidine, and melicopicine and the furoquinolines skimmianine, acronycidine, and kokusaginine, the structures of which have all been established previously. In addition two new alkaloids are present. These are 2,4-dimethoxy-10-methylacridone (I) and a dimethoxydimethylpyranofuroquinoline which has been named acronidine. Acronidine has been degraded to a phenol which on methylation gives isokokusaginine (II). The alkaloid must therefore possess structure III or IV, the latter being preferred.

  Acronychia baueri Schott. 含有吖啶生物碱 melicopine、melicopidine 和 melicopicine 以及呋喃喹啉类 skimmianine、acronycidine 和 kokusaginine。 呋喃喹啉类的 Skimmianine、acronycidine 和 kokusaginine。 这些生物碱的结构以前都已确定。此外，还发现了两种新生物碱。 新生物碱。它们是 2,4-二甲氧基-10-甲基吖啶酮（I）和一种 被命名为 Acronidine 的二甲氧基二甲基吡喃呋喃喹啉。 阿克罗啶被降解为一种苯酚，甲基化后可得到 异木香碱 (II)。因此，生物碱必须具有结构 III 或 IV、 后者更可取。
• Batterham,T.J.; Lamberton,J.A., Australian Journal of Chemistry, 1965, vol. 18, p. 859 - 866
  作者：Batterham,T.J.、Lamberton,J.A.

  DOI：——

  日期：——
• Eastwood et al., Australian Journal of Chemistry, 1954, vol. 7, p. 87,93
  作者：Eastwood et al.

  DOI：——

  日期：——
• Deulofeu; Bassi, Anales des la Asociacion Quimica Argentina, <hi>1952</hi>, vol. 40, p. 249,254
  作者：Deulofeu、Bassi

  DOI：——

  日期：——
• 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.