LG120746 | 179895-46-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: LG120746
• 英文别名: 5-(3-chlorophenyl)-9-fluoro-2,2,4-trimethyl-1,5-dihydrochromeno[3,4-f]quinoline
• CAS: 179895-46-6
• 化学式: C₂₅H₂₁ClFNO
• 分子量: 405.899
• InChiKey: OHLMRBMVXRKABN-UHFFFAOYSA-N

物化性质

• 沸点：
  556.1±50.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  29
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  LG120746 生成 5-(3-Chloro-phenyl)-9-fluoro-2,2,4-trimethyl-2,5-dihydro-1H-6-oxa-1-aza-chrysene
  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：

  间氯溴苯 在 三乙基硅烷 、 正丁基锂 、 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 LG120746
  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

文献信息

• 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.
• US6268497B1
  申请人：——

  公开号：US6268497B1

  公开（公告）日：2001-07-31
• 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.