5'-cyano-2'-hydroxy-3-[2-(2-quinolinyl)ethenyl]chalcone | 780018-29-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 5'-cyano-2'-hydroxy-3-[2-(2-quinolinyl)ethenyl]chalcone
• 英文别名: 4-Hydroxy-3-(3-(3-(2-(quinolin-2-yl)vinyl)phenyl)acryloyl)benzonitrile；4-hydroxy-3-[(E)-3-[3-[(E)-2-quinolin-2-ylethenyl]phenyl]prop-2-enoyl]benzonitrile
• CAS: 780018-29-3
• 化学式: C₂₇H₁₈N₂O₂
• 分子量: 402.452
• InChiKey: RHGRRGBOSFJRBE-MXOVAJDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5'-cyano-2'-hydroxy-3-[2-(2-quinolinyl)ethenyl]chalcone 在 selenium(IV) oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 8.0h， 以39%的产率得到4-Oxo-2-[3-((E)-2-quinolin-2-yl-vinyl)-phenyl]-4H-chromene-6-carbonitrile
  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
• 作为产物：
  描述：

  间苯二甲醛 在 氢氧化钾 、 乙酸酐 作用下， 以 四氢呋喃 、 乙醇 、 xylene 为溶剂， 反应 175.0h， 生成 5'-cyano-2'-hydroxy-3-[2-(2-quinolinyl)ethenyl]chalcone
  参考文献：
  名称：

  羧基查耳酮的合成与构效关系：CysLT1（LTD4）受体拮抗剂的新系列。

  摘要：

  一系列新的2-，3-和4-（2-喹啉基甲氧基）-和3-和4- [2-（2-喹啉基）乙烯基]-取代的2'-，3的合成及CysLT1拮抗活性描述了'-，4'-或5'-羧基查耳酮。结构-活性关系研究表明，优选带负电的（酸性）部分，尽管在某些情况下腈或酯类似物也具有中等活性。喹啉部分可以在3-或4-位被取代。用其他芳香族基团取代该杂环会导致化合物具有可比的亲和力[2-（7-氯喹啉），1-（1-甲基-2-苯并咪唑）或1-（2-苯并噻唑）]或具有较低的活性[1 -（1-乙氧基乙基）-2-苯并咪唑，2-萘基或苯基]。喹啉和查耳酮部分可以通过乙烯基或甲氧基间隔基连接。对于3-和4-取代的查耳酮，查耳酮B环上的酸性部分可以连接至2'-，3'-，4'-或5'-位置。没有一般模式可以指定哪个取代位置产生最有效的化合物。该系列包含几种有效的CysLT1受体拮抗剂，其K（D）值接近纳摩尔范围，通过[3H] LTD4

  DOI：

  10.1021/jm960628d

文献信息

• CHALCONE DERIVATIVES AND DRUGS CONTAINING THE SAME
  申请人：KOWA CO. LTD.

  公开号：EP0902007A1

  公开（公告）日：1999-03-17

  This invention relates to chalcone derivatives represented by the following formula (1): wherein A represents a phenyl group, a quinolyl group or the like, W represents a vinylene group or the like, and R1 to R5 each independently represent a carboxyl, cyano, alkyloxycarbonyl or like group, or salts of the chalcone derivatives, and also to drugs containing them as effective ingredients. These compounds have excellent cys-LT receptor antagonism, and are useful as antiallergic agents or the like.

  本发明涉及下式（1）所代表的查尔酮衍生物： 其中 A 代表苯基、喹啉基或类似基团，W 代表乙烯基或类似基团，R1 至 R5 各自独立地代表羧基、氰基、烷氧基羰基或类似基团，或查尔酮衍生物的盐，还涉及含有它们作为有效成分的药物。 这些化合物具有优异的 cys-LT 受体拮抗作用，可用作抗过敏剂或类似药物。
• Synthesis and Structure−Activity Relationships of Carboxylated Chalcones:  A Novel Series of <i>CysLT</i>₁ (LTD₄) Receptor Antagonists
  作者：Mariël E. Zwaagstra、Hendrik Timmerman、Masahiro Tamura、Tsutomu Tohma、Yasushi Wada、Kazuhiro Onogi、Ming-Qiang Zhang

  DOI：10.1021/jm960628d

  日期：1997.3.1

  The synthesis and CysLT1 antagonistic activities of a new series of 2-, 3-, and 4-(2-quinolinylmethoxy)- and 3- and 4-[2-(2-quinolinyl)ethenyl]-substituted, 2'-, 3'-, 4'-, or 5'-carboxylated chalcones are described. Structure-activity relationship studies indicate a preference for the presence of a negatively charged (acidic) moiety, although in some cases nitrile or ester analogues also exhibit moderate

  一系列新的2-，3-和4-（2-喹啉基甲氧基）-和3-和4- [2-（2-喹啉基）乙烯基]-取代的2'-，3的合成及CysLT1拮抗活性描述了'-，4'-或5'-羧基查耳酮。结构-活性关系研究表明，优选带负电的（酸性）部分，尽管在某些情况下腈或酯类似物也具有中等活性。喹啉部分可以在3-或4-位被取代。用其他芳香族基团取代该杂环会导致化合物具有可比的亲和力[2-（7-氯喹啉），1-（1-甲基-2-苯并咪唑）或1-（2-苯并噻唑）]或具有较低的活性[1 -（1-乙氧基乙基）-2-苯并咪唑，2-萘基或苯基]。喹啉和查耳酮部分可以通过乙烯基或甲氧基间隔基连接。对于3-和4-取代的查耳酮，查耳酮B环上的酸性部分可以连接至2'-，3'-，4'-或5'-位置。没有一般模式可以指定哪个取代位置产生最有效的化合物。该系列包含几种有效的CysLT1受体拮抗剂，其K（D）值接近纳摩尔范围，通过[3H] LTD4
• Synthesis and Structure−Activity Relationships of Carboxyflavones as Structurally Rigid <i>CysLT</i><i>₁</i> (LTD₄) Receptor Antagonists
  作者：Mariël E. Zwaagstra、Henk Timmerman、Andrea C. van de Stolpe、Frans J. J. de Kanter、Masahiro Tamura、Yasushi Wada、Ming-Qiang Zhang

  DOI：10.1021/jm970179x

  日期：1998.4.1

  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.