(Z)-2-(4-chlorobenzylidene)-6-methoxybenzofuran-3(2H)-one | 139276-17-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 橙酮类黄酮
• 英文名称: (Z)-2-(4-chlorobenzylidene)-6-methoxybenzofuran-3(2H)-one
• 英文别名: 2-(p-chlorobenzylidene)-6-methoxy-3(2H)-benzofuranone；(2Z)-2-[(4-chlorophenyl)methylidene]-6-methoxy-1-benzofuran-3-one
• CAS: 139276-17-8
• 化学式: C₁₆H₁₁ClO₃
• 分子量: 286.715
• InChiKey: VWGPEPCJDXBXEM-NVNXTCNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (Z)-2-(4-chlorobenzylidene)-6-methoxybenzofuran-3(2H)-one 在 palladium on activated charcoal 正丁基锂 、 氢气 作用下， 以 乙酸乙酯 为溶剂， -78.0~25.0 ℃ 、101.33 kPa 条件下， 反应 18.5h， 生成 2-(4-Chloro-benzyl)-6-methoxy-3-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-2,3-dihydro-benzofuran-3-ol
  参考文献：
  名称：

  Synthesis of 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans as selective ligands for antiestrogen-binding sites. Effects on cell proliferation and cholesterol synthesis

  摘要：

  A series of nonsteroidal compounds, 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans derived from the 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones has been synthesized. The key steps in the synthesis were reactions of 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones with the arylorganometallic reagents followed by dehydration of the resulting carbinols. The benzofurans are ligands for antiestrogen-binding sites (AEBS) and display no significant interaction with the estrogen receptor (ER). All bind to AEBS with equivalent or greater affinity than tamoxifen. These compounds decrease [H-3]thymidine incorporation in AEBS-containing EL4 lymphoid cells and MCF7 breast cancer cells in a concentration-dependent manner between 10(-8) and 10(-6) M and are generally more inhibitory than tamoxifen. In contrast, they have no effect on [H-3]thymidine incorporation by an AEBS-deficient variant of the MCF7 cell line, RTx6. The present findings of (1) selective and high affinity binding of the benzofurans to AEBS, (2) their concentration-dependent inhibition of [H-3]thymidine incorporation in AEBS-containing cells, and (3) their lack of antiproliferative effect in an AEBS-deficient cell line suggest a functional role for AEBS in mediating the antigrowth effect of these compounds. Two of the more active benzofuran compounds also significantly inhibited de novo cholesterol biosynthesis in EL4 cells which lack ER. This effect could be obtained after 5 h of treatment and preceded significant loss of cell viability. This is the first demonstration that selective ligands of AEBS (other than the known nonsteroidal antiestrogens) interfere with cholesterol biosynthesis-an action that may contribute to their antigrowth effect.

  DOI：

  10.1021/jm00086a002
• 作为产物：
  描述：

  6-羟基-2H-苯并呋喃-3-酮 在 盐酸 、 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 6.0h， 生成 (Z)-2-(4-chlorobenzylidene)-6-methoxybenzofuran-3(2H)-one
  参考文献：
  名称：

  Synthesis of 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans as selective ligands for antiestrogen-binding sites. Effects on cell proliferation and cholesterol synthesis

  摘要：

  A series of nonsteroidal compounds, 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans derived from the 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones has been synthesized. The key steps in the synthesis were reactions of 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones with the arylorganometallic reagents followed by dehydration of the resulting carbinols. The benzofurans are ligands for antiestrogen-binding sites (AEBS) and display no significant interaction with the estrogen receptor (ER). All bind to AEBS with equivalent or greater affinity than tamoxifen. These compounds decrease [H-3]thymidine incorporation in AEBS-containing EL4 lymphoid cells and MCF7 breast cancer cells in a concentration-dependent manner between 10(-8) and 10(-6) M and are generally more inhibitory than tamoxifen. In contrast, they have no effect on [H-3]thymidine incorporation by an AEBS-deficient variant of the MCF7 cell line, RTx6. The present findings of (1) selective and high affinity binding of the benzofurans to AEBS, (2) their concentration-dependent inhibition of [H-3]thymidine incorporation in AEBS-containing cells, and (3) their lack of antiproliferative effect in an AEBS-deficient cell line suggest a functional role for AEBS in mediating the antigrowth effect of these compounds. Two of the more active benzofuran compounds also significantly inhibited de novo cholesterol biosynthesis in EL4 cells which lack ER. This effect could be obtained after 5 h of treatment and preceded significant loss of cell viability. This is the first demonstration that selective ligands of AEBS (other than the known nonsteroidal antiestrogens) interfere with cholesterol biosynthesis-an action that may contribute to their antigrowth effect.

  DOI：

  10.1021/jm00086a002

文献信息

• 2-(benzyl)-3-arylbenzofurans as antitumour and hypocholesterolemic agents
  申请人：National University of Singapore

  公开号：US05354861A1

  公开（公告）日：1994-10-11

  The synthesis and the biological evaluation of a series of basic ethers of 2-benzyl-3-arylbenzofurans as antitumor agents is described. These compounds bind significantly to the antiestrogen-binding sites but only poorly to the estrogen receptor sites and are cytotoxic to tumor cells. Some of these compounds also significantly inhibited de novo cholesterol biosynthesis in an estrogen receptor negative lymphoma cell line rich in antiestrogen-binding sites.

  描述了一系列2-苄基-3-芳基苯并呋喃的碱性醚类化合物的合成和生物评价作为抗肿瘤药物。这些化合物显著结合到抗雌激素结合位点，但对雌激素受体位点的结合较弱，并且对肿瘤细胞具有细胞毒性。其中一些化合物还显著抑制了富含抗雌激素结合位点的雌激素受体阴性淋巴瘤细胞系中的新生胆固醇生物合成。
• ——
  作者：A. M. Shestopalov、O. A. Naumov

  DOI：10.1023/a:1024468813689

  日期：——

  The reactions of 6-methoxybenzo[b]furan-3(2H)-one with 2-aryl-1,1-dicyanoethylenes and malononitrile or with aromatic aldehyde and two moles of malononitrile afford 2-amino-4-aryl-1,3-dicyano-7-methoxydibenzo[b,d]ftirans. The reactions of benzo[b]thiophen-3(2H)one with 2-aryl-1,1-dicyanoethylenes or with aromatic aldehyde and one mole of malononitrile produce 2-amino-4-aryi-3-cyano-4H-benzothieno[3,2-b]pyrans.
• 10.3998/ark.5550190.p009.918
  作者：Venkateswarlu, Somepalli、Murty, Gandrotu Narasimha、Satyanarayana, Meka

  DOI：10.3998/ark.5550190.p009.918

  日期：——
• "On water" synthesis of aurones: first synthesis of 4,5,3',4',5'-pentamethoxy-6-hydroxyaurone from Smilax riparia
  作者：Somepalli Venkateswarlu、Gandrotu Narasimha Murty、Meka Satyanarayana

  DOI：10.24820/ark.5550190.p009.918

  日期：——
• US5354861A
  申请人：——

  公开号：US5354861A

  公开（公告）日：1994-10-11