3-[2-(phthalimido)ethoxy]-8-[2-(phthalimido)ethoxycarbonyl]4'-[(2-quinolinyl)methoxy]flavone | 205875-23-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 3-[2-(phthalimido)ethoxy]-8-[2-(phthalimido)ethoxycarbonyl]4'-[(2-quinolinyl)methoxy]flavone
• 英文别名: 2-(1,3-Dioxoisoindol-2-yl)ethyl 3-[2-(1,3-dioxoisoindol-2-yl)ethoxy]-4-oxo-2-[4-(quinolin-2-ylmethoxy)phenyl]chromene-8-carboxylate
• CAS: 205875-23-6
• 化学式: C₄₆H₃₁N₃O₁₀
• 分子量: 785.766
• InChiKey: SQWOPXIVMXITIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  59
• 可旋转键数：
  13
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  159
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  3-[2-(phthalimido)ethoxy]-8-[2-(phthalimido)ethoxycarbonyl]4'-[(2-quinolinyl)methoxy]flavone 在 lithium hydroxide 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 3.0h， 生成 3-(2-Amino-ethoxy)-4-oxo-2-[4-(quinolin-2-ylmethoxy)-phenyl]-4H-chromene-8-carboxylic acid
  参考文献：
  名称：

  Synthesis of 3-and 5′-substituted flavone-8-carboxylic acids as ‘three-armed’ leukotriene CysLT1 receptor antagonists

  摘要：

  Molecular modelling of leukotriene CysLT(1) receptor antagonists have suggested that in addition to the two binding sites for a lipophilic and an acidic group, the receptor has a 'third pocket' to accommodate 'three-armed' ligands such as montelukast 1. Based on the most rigid CysLT(1) receptor antagonist 3'-[2-(2-quinolinyl)ethenyl]flavone-8-carboxylic acid 2, we have synthesised 3- and 5'-substituted flavone derivatives to probe this additional binding pocket. Introduction of large substituents, e.g. 2-quinolinyl-methoxy, to the C5' position of the flavone skeleton abolished the CysLT(1) receptor affinity whereas the same modification at the C3 position yielded a potent CysLT antagonist. This observation implies that the third binding pocket of the receptor has considerable steric tolerance, probably corresponding to the substituents at C3 of the flavone skeleton. Further modification by introducing a C3 substituent containing a basic nitrogen resulted in compound 6g with potent H-1 antihistaminic activity although the CysLT(1) antagonistic activity was much reduced. Further study on the CysLT(1) receptor recognition of three armed antagonists may facilitate the design of more effective antiasthmatic agents, e.g. dual antagonists of histamine H-1 and leukotriene CysLT(1) receptors. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80034-2
• 作为产物：
  描述：

  N-(2-溴乙基)邻苯二甲酰亚胺 、 8-carboxy-3-hydroxy-4'-[(2-quinolinyl)methoxy]flavone 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以62%的产率得到3-[2-(phthalimido)ethoxy]-8-[2-(phthalimido)ethoxycarbonyl]4'-[(2-quinolinyl)methoxy]flavone
  参考文献：
  名称：

  Flavone derivative and medicine comprising the same

  摘要：

  本发明涉及一种由式（1）表示的黄酮衍生物或其盐，以及包含该衍生物的药物。其中A代表H，卤素，苯基，萘基，式（2）中的一个基团，其中X为H或卤素，B为--CH.dbd.CH--，--CH.dbd.N--，--N(R.sup.7)--（R.sup.7：低碳基或烷氧基烷基），--O--或--S--；W代表单键，--CH.sub.2 O--或--CH.dbd.CH--；R.sup.1至R.sup.4中的至少一个代表--COOH，--CN，烷氧羰基，四唑基或--CONHR.sup.8（R.sup.8：H，低碳基或苯基磺酰基），其余各自代表H，卤素，--OH，低碳基或低烷氧基；R.sup.5代表H，--OH，低烷氧基，--O(CH.sub.2).sub.m NR.sup.9 R.sup.10（R.sup.9，R.sup.10：H或低碳基，或与相邻的N结合形成邻苯二甲酰亚胺基；m：1-5），或式（3）中的一个基团（n：1-5，l：2-3；R.sup.6代表H，卤素，低碳基或低烷氧基。排除A为H或卤素，W为单键且R.sup.5为H的情况。该化合物（1）具有优异的cys-LT.sub.1受体拮抗作用。

  公开号：

  US06136848A1

文献信息

• US6136848A
  申请人：——

  公开号：US6136848A

  公开（公告）日：2000-10-24
• Flavone derivative and medicine comprising the same
  申请人：Kowa Co., Ltd.

  公开号：US06136848A1

  公开（公告）日：2000-10-24

  This invention relates to a flavone derivative represented by the formula (1) or a salt thereof, and also to a medicine containing the same. ##STR1## wherein A represents H, halogen, phenyl, naphthyl, a group of the formula (2) in which X is H or halogen, B is --CH.dbd.CH--, --CH.dbd.N--, --N(R.sup.7)-- (R.sup.7 : lower alkyl or alkoxyalkyl), --O-- or --S--; W represents a single bond, --CH.sub.2 O-- or --CH.dbd.CH--; at least one of R.sup.1 to R.sup.4 represents --COOH, --CN, alkyloxycarbonyl, tetrazolyl or --CONHR.sup.8 (R.sup.8 : H, lower alkyl or phenylsulfonyl), the remainder thereof individually represent H, halogen, --OH, lower alkyl or lower alkoxyl; R.sup.5 represents H, --OH, lower alkoxyl, --O(CH.sub.2).sub.m NR.sup.9 R.sup.10 (R.sup.9,R.sup.10 : H or lower alkyl, or coupled together with the adjacent N to form a phthalimido group; m: 1-5), or a group of the formula (3) (n: 1-5, l: 2-3; and R.sup.6 represents H, halogen, lower alkyl or lower alkoxyl. A situation where A is H or halogen, W is a single bond and R.sup.5 is H is excluded. The compound (1) has excellent cys-LT.sub.1 receptor antagonism.

  本发明涉及一种由式（1）表示的黄酮衍生物或其盐，以及包含该衍生物的药物。其中A代表H，卤素，苯基，萘基，式（2）中的一个基团，其中X为H或卤素，B为--CH.dbd.CH--，--CH.dbd.N--，--N(R.sup.7)--（R.sup.7：低碳基或烷氧基烷基），--O--或--S--；W代表单键，--CH.sub.2 O--或--CH.dbd.CH--；R.sup.1至R.sup.4中的至少一个代表--COOH，--CN，烷氧羰基，四唑基或--CONHR.sup.8（R.sup.8：H，低碳基或苯基磺酰基），其余各自代表H，卤素，--OH，低碳基或低烷氧基；R.sup.5代表H，--OH，低烷氧基，--O(CH.sub.2).sub.m NR.sup.9 R.sup.10（R.sup.9，R.sup.10：H或低碳基，或与相邻的N结合形成邻苯二甲酰亚胺基；m：1-5），或式（3）中的一个基团（n：1-5，l：2-3；R.sup.6代表H，卤素，低碳基或低烷氧基。排除A为H或卤素，W为单键且R.sup.5为H的情况。该化合物（1）具有优异的cys-LT.sub.1受体拮抗作用。
• Synthesis of 3-and 5′-substituted flavone-8-carboxylic acids as ‘three-armed’ leukotriene CysLT1 receptor antagonists
  作者：Mariël E. Zwaagstra、Ronald E.M. Korthouwer、Henk Timmerman、Ming-Qiang Zhang

  DOI：10.1016/s0223-5234(98)80034-2

  日期：1998.2

  Molecular modelling of leukotriene CysLT(1) receptor antagonists have suggested that in addition to the two binding sites for a lipophilic and an acidic group, the receptor has a 'third pocket' to accommodate 'three-armed' ligands such as montelukast 1. Based on the most rigid CysLT(1) receptor antagonist 3'-[2-(2-quinolinyl)ethenyl]flavone-8-carboxylic acid 2, we have synthesised 3- and 5'-substituted flavone derivatives to probe this additional binding pocket. Introduction of large substituents, e.g. 2-quinolinyl-methoxy, to the C5' position of the flavone skeleton abolished the CysLT(1) receptor affinity whereas the same modification at the C3 position yielded a potent CysLT antagonist. This observation implies that the third binding pocket of the receptor has considerable steric tolerance, probably corresponding to the substituents at C3 of the flavone skeleton. Further modification by introducing a C3 substituent containing a basic nitrogen resulted in compound 6g with potent H-1 antihistaminic activity although the CysLT(1) antagonistic activity was much reduced. Further study on the CysLT(1) receptor recognition of three armed antagonists may facilitate the design of more effective antiasthmatic agents, e.g. dual antagonists of histamine H-1 and leukotriene CysLT(1) receptors. (C) Elsevier, Paris.