6-{[2-(1,1'-biphenyl-4-yl)-2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl]methoxy}-3,4-dihydroquinolin-2(1H)-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-{[2-(1,1'-biphenyl-4-yl)-2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl]methoxy}-3,4-dihydroquinolin-2(1H)-one
• 英文别名: 6-[[4-methylidene-5-oxo-2-(4-phenylphenyl)oxolan-2-yl]methoxy]-3,4-dihydro-1H-quinolin-2-one
• 化学式: C₂₇H₂₃NO₄
• 分子量: 425.484
• InChiKey: AJEYNHVEMXISJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-羟基-3,4-二氢-2(1H)-喹诺酮 在 potassium carbonate 、 锌 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 6-{[2-(1,1'-biphenyl-4-yl)-2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl]methoxy}-3,4-dihydroquinolin-2(1H)-one
  参考文献：
  名称：

  Synthesis and Antiplatelet-Activity Evaluation ofα-Methylidene-γ-butyrolactones Bearing 3,4-Dihydroquinolin-2(1H)-one Moieties

  摘要：

  In continuation of our search for potent antiplatelet agents, we have synthesized and evaluated several alpha-methylidene-gamma-butyrolactones hearing 3,4-dihydroquinolin-2(1H)-one moieties. O-Alkylation of 3,4-dihydro-8-hydroxyquinolin-2(1H)-one (1) with chloroacetone under basic conditions afforded 3,4-dihydro-8-(2-oxopropoxy)quinolin-2(1H)-one (2a) and tricyclic 2,3,6,7-tetrahydro-3-hydroxy-3-methyl-5H-pyrido[1,2,3-de][1,4]- benzoxazin-5-one (3a) in a ratio of 1 : 2.84. Their Reformatsky-type condensation with ethyl 2-(bromomethyl)- prop-2-enoate furnished 3,4-dihydro-8-[(2,3,4,5-tetrahydro-2-methyl-4-methylidene-5-oxofuran-2-yl)methoxy]-quinolin-2(1H)-one (4a), which shows antiplatelet activity, in 70% yield. Its 2'-Ph derivatives, and 6- and 7- substituted analogs were also obtained from the corresponding 3,4-dihydroquinolin-2(1H)-ones via alkylation and the Reformatsky-type condensation. Of these compounds, 3,4-dihydro-7-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-phenylfuran-2-yl)methoxy] (10b) was the most active against arachidonic acid (AA) induced platelet aggregation with an IC(50) of 0.23 mu M. For the inhibition of platelet-activating factor (PAF) induced aggregation. 6-{[2-(4-fluorophenyl)-2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl]methoxy}-3,4-dihydroquinolin-2(1H)-one (9c) was the most potent with an IC(50) value of 1.83 mu M.

  DOI：

  10.1002/(sici)1522-2675(20000216)83:2<349::aid-hlca349>3.0.co;2-b

文献信息

• Synthesis and Antiplatelet-Activity Evaluation ofα-Methylidene-γ-butyrolactones Bearing 3,4-Dihydroquinolin-2(1H)-one Moieties
  作者：Cherng-Chyi Tzeng、I.-Li Chen、Yeh-Long Chen、Tai-Chi Wang、Ya-Ling Chang、Che-Ming Teng

  DOI：10.1002/(sici)1522-2675(20000216)83:2<349::aid-hlca349>3.0.co;2-b

  日期：2000.2.16

  In continuation of our search for potent antiplatelet agents, we have synthesized and evaluated several alpha-methylidene-gamma-butyrolactones hearing 3,4-dihydroquinolin-2(1H)-one moieties. O-Alkylation of 3,4-dihydro-8-hydroxyquinolin-2(1H)-one (1) with chloroacetone under basic conditions afforded 3,4-dihydro-8-(2-oxopropoxy)quinolin-2(1H)-one (2a) and tricyclic 2,3,6,7-tetrahydro-3-hydroxy-3-methyl-5H-pyrido[1,2,3-de][1,4]- benzoxazin-5-one (3a) in a ratio of 1 : 2.84. Their Reformatsky-type condensation with ethyl 2-(bromomethyl)- prop-2-enoate furnished 3,4-dihydro-8-[(2,3,4,5-tetrahydro-2-methyl-4-methylidene-5-oxofuran-2-yl)methoxy]-quinolin-2(1H)-one (4a), which shows antiplatelet activity, in 70% yield. Its 2'-Ph derivatives, and 6- and 7- substituted analogs were also obtained from the corresponding 3,4-dihydroquinolin-2(1H)-ones via alkylation and the Reformatsky-type condensation. Of these compounds, 3,4-dihydro-7-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-phenylfuran-2-yl)methoxy] (10b) was the most active against arachidonic acid (AA) induced platelet aggregation with an IC(50) of 0.23 mu M. For the inhibition of platelet-activating factor (PAF) induced aggregation. 6-[2-(4-fluorophenyl)-2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl]methoxy}-3,4-dihydroquinolin-2(1H)-one (9c) was the most potent with an IC(50) value of 1.83 mu M.