2-Fluoro-8-nitrobenzo[c]chromen-6-one | 179898-11-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 2-Fluoro-8-nitrobenzo[c]chromen-6-one
• CAS: 179898-11-4
• 化学式: C₁₃H₆FNO₄
• 分子量: 259.193
• InChiKey: VPZSLIXOMXKRFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-Fluoro-8-nitrobenzo[c]chromen-6-one 在 calcium chloride 、 锌 作用下， 以 乙醇 为溶剂， 反应 15.0h， 以93%的产率得到8-Amino-2-fluorobenzo[c]chromen-6-one
  参考文献：
  名称：

  Preparation, Resolution, and Biological Evaluation of 5-Aryl-1,2-dihydro-5H-chromeno[3,4-f]quinolines:  Potent, Orally Active, Nonsteroidal Progesterone Receptor Agonists

  摘要：

  Two potent nonsteroidal progestins from the 5-aryl-1,2-dihydro-5H-chromeno[3,4-f]quinoline class (LG120746 and LG120747) were selected for scale-up, resolution, and biological evaluation of the purified enantiomers. For each quinoline, the levorotatory enantiomer was determined to be the more potent agonist of the human progesterone receptor isoform B (hPR-B) (EC50 < 3 nM), but the dextrorotatory enantiomers retained significant PR modulatory activity (EC50 < 200 nM). In two in vivo rodent models of progestational activity, a pregnancy maintenance assay and a uterine wet weight assay, the two eutomers displayed potent progesterone-like effects. In a third model for progestational activity, the mammary end bud assay, these compounds were significantly less active. These studies demonstrate that certain members of this class of selective progesterone receptor modulators display encouraging and potentially useful tissue-selective progestational effects.

  DOI：

  10.1021/jm980190c
• 作为产物：
  描述：

  methyl (5'-fluoro-2'-methoxy-4-nitro-2-biphenyl)carboxylate 在 氢氧化钾 、 三氯化铝 、 氯化亚砜 作用下， 以 四氢呋喃 、 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 6.5h， 生成 2-Fluoro-8-nitrobenzo[c]chromen-6-one
  参考文献：
  名称：

  5-Aryl-1,2-dihydro-5H-chromeno[3,4-f]quinolines as Potent, Orally Active, Nonsteroidal Progesterone Receptor Agonists:  The Effect of D-Ring Substituents

  摘要：

  Several 5-(4-chlorophenyl)-1,2-dihydro-5H-chromeno[3,4-f]quinolines were prepared to determine the effects of substitution at C(8) and C(9) on the progestational activity of this pharmacophore. In combination with a halogen (F or Cl) at C(9), replacement of the C(5) aryl group with variously substituted aryl groups resulted in optimization of the progestational activity, affording compounds with in vitro activity greater than that of progesterone as measured by a cotransfection assay using human progesterone receptor subtype-B (hPR-B). Binding affinities (K-i) to hPR-A were subnanomolar in many cases. These in vitro effects were verified in vivo using a rodent model. Compound 10 (LG120794, 9-chloro-5-(4-chlorophenyl)-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline] was more potent than medroxyprogesterone acetate at counterpoising the effects of estradiol benzoate in the uterine wet weight assay using immature rats.

  DOI：

  10.1021/jm9705770

文献信息

• Preparation, Resolution, and Biological Evaluation of 5-Aryl-1,2-dihydro-5<i>H</i>-chromeno[3,4-<i>f</i>]quinolines:  Potent, Orally Active, Nonsteroidal Progesterone Receptor Agonists
  作者：James P. Edwards、Lin Zhi、Charlotte L. F. Pooley、Christopher M. Tegley、Sarah J. West、Ming-Wei Wang、Marco M. Gottardis、Charles Pathirana、William T. Schrader、Todd K. Jones

  DOI：10.1021/jm980190c

  日期：1998.7.1

  Two potent nonsteroidal progestins from the 5-aryl-1,2-dihydro-5H-chromeno[3,4-f]quinoline class (LG120746 and LG120747) were selected for scale-up, resolution, and biological evaluation of the purified enantiomers. For each quinoline, the levorotatory enantiomer was determined to be the more potent agonist of the human progesterone receptor isoform B (hPR-B) (EC50 < 3 nM), but the dextrorotatory enantiomers retained significant PR modulatory activity (EC50 < 200 nM). In two in vivo rodent models of progestational activity, a pregnancy maintenance assay and a uterine wet weight assay, the two eutomers displayed potent progesterone-like effects. In a third model for progestational activity, the mammary end bud assay, these compounds were significantly less active. These studies demonstrate that certain members of this class of selective progesterone receptor modulators display encouraging and potentially useful tissue-selective progestational effects.
• 5-Aryl-1,2-dihydro-5<i>H</i>-chromeno[3,4-<i>f</i>]quinolines as Potent, Orally Active, Nonsteroidal Progesterone Receptor Agonists:  The Effect of D-Ring Substituents
  作者：James P. Edwards、Sarah J. West、Keith B. Marschke、Dale E. Mais、Marco M. Gottardis、Todd K. Jones

  DOI：10.1021/jm9705770

  日期：1998.1.1

  Several 5-(4-chlorophenyl)-1,2-dihydro-5H-chromeno[3,4-f]quinolines were prepared to determine the effects of substitution at C(8) and C(9) on the progestational activity of this pharmacophore. In combination with a halogen (F or Cl) at C(9), replacement of the C(5) aryl group with variously substituted aryl groups resulted in optimization of the progestational activity, affording compounds with in vitro activity greater than that of progesterone as measured by a cotransfection assay using human progesterone receptor subtype-B (hPR-B). Binding affinities (K-i) to hPR-A were subnanomolar in many cases. These in vitro effects were verified in vivo using a rodent model. Compound 10 (LG120794, 9-chloro-5-(4-chlorophenyl)-1,2-dihydro-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline] was more potent than medroxyprogesterone acetate at counterpoising the effects of estradiol benzoate in the uterine wet weight assay using immature rats.
• Development of progesterone receptor antagonists from 1,2-dihydrochromeno[3,4-f]quinoline agonist pharmacophore
  作者：Lin Zhi、Josef D Ringgenberg、James P Edwards、Christopher M Tegley、Sarah J West、Barbara Pio、Mehrnouch Motamedi、Todd K Jones、Keith B Marschke、Dale E Mais、William T Schrader

  DOI：10.1016/s0960-894x(03)00256-7

  日期：2003.6

  A series of 1,2-dihydrochromeno[3,4-f]quinoline derivatives was synthesized and tested in biological assays to evaluate the nonsteroidal progesterone receptor modulator pharmacophore (4) as antiprogestins. A number of potent analogues were identified by modification of the substituents at the D-ring. (C) 2003 Elsevier Science Ltd. All rights reserved.