8-ethoxycarbonyl-3'-[(2-quinolinyl)methoxy]flavone | 205045-47-2

• 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: 8-ethoxycarbonyl-3'-[(2-quinolinyl)methoxy]flavone
• 英文别名: Ethyl 4-oxo-2-[3-(quinolin-2-ylmethoxy)phenyl]chromene-8-carboxylate
• CAS: 205045-47-2
• 化学式: C₂₈H₂₁NO₅
• 分子量: 451.478
• InChiKey: PIHYQBCQRPXHFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  74.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-ethoxycarbonyl-3'-[(2-quinolinyl)methoxy]flavone 以40%的产率得到8-carboxy-3'-(2-quinolinylmethoxy)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
• 作为产物：
  描述：

  3-[(E)-3-(3-Benzyloxy-phenyl)-acryloyl]-2-hydroxy-benzoic acid 在 palladium on activated charcoal selenium(IV) oxide 、 ammonium formate 、 sodium hydride 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 56.5h， 生成 8-ethoxycarbonyl-3'-[(2-quinolinyl)methoxy]flavone
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Carboxyflavones as Structurally Rigid CysLT₁ (LTD₄) Receptor Antagonists

  摘要：

  The synthesis and CysLT(1) receptor affinities of a new series of highly rigid 3'- and 4'-(2-quinolinylmethoxy)- or 3'- and 4'-[2-(2-quinolinyl)ethenyl]-substituted 6-, 7-, or 8-carboxylated flavones are described. CysLT(1) receptor affinities of the flavones (down to 11 nM) were determined by their ability to displace [H-3]LTD4 from its receptor in guinea pig lung membranes. Structure-affinity relationship studies showed that the relative positions of the carboxylic acid and the quinoline moiety were critical for CysLT(1) affinities. While the carboxyl is optimal in the 8 position but tolerated in the 6 position, only the 6- and not the 8-tetrazole has significant activity. The quinoline moiety may be connected to the flavone skeleton by an ethenyl or a methoxy linker, but the substitution position is important for high affinity, especially in the 6-carboxylated flavones. 4'-Substituted 6-carboxyflavones are essentially inactive, whereas the 3'-substituted analogues have submicromolar CysLT(1) affinity. Replacement of the quinoline by other heteroaromates generally leads to decreased affinities, with the phenyl and naphthyl analogues displaying only little or no affinity, while the 7-chloroquinoline analogue is comparable in activity to the quinoline. Flavones having CysLT(1) receptor affinities of 10-30 nM were selected for determination of their inhibitory effects on the LTD4-induced contraction of guinea pig ileum in vitro. The IC50 values ranged between 15 and 100 nM. Compound 5d (8-carboxy-6-chloro-3'-(2-quinolinylmethoxy)flavone, VUF 5087) was selected for further research because of its high potency in the functional assay. This series contains the most rigid CysLT(1) receptor antagonists known to date, and they are useful in the development of a CysLT(1) antagonist model, which is discussed in the companion paper.

  DOI：

  10.1021/jm970179x

文献信息

• US6136848A
  申请人：——

  公开号：US6136848A

  公开（公告）日：2000-10-24