1,2-Dihydro-2,2,4-trimethyl-5-[3-(trifluoromethyl)phenyl]-5H-chromeno[3,4-f]quinoline | 179895-29-5

• 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: 1,2-Dihydro-2,2,4-trimethyl-5-[3-(trifluoromethyl)phenyl]-5H-chromeno[3,4-f]quinoline
• 英文别名: 2,2,4-Trimethyl-5-(3-trifluoromethyl-phenyl)-2,5-dihydro-1H-6-oxa-1-aza-chrysene；2,2,4-trimethyl-5-[3-(trifluoromethyl)phenyl]-1,5-dihydrochromeno[3,4-f]quinoline
• CAS: 179895-29-5
• 化学式: C₂₆H₂₂F₃NO
• 分子量: 421.462
• InChiKey: CTCHAYJBEBAVDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  31
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,2-Dihydro-2,2,4-trimethyl-5-[3-(trifluoromethyl)phenyl]-5H-chromeno[3,4-f]quinoline 在 正丁基锂 、 硼烷四氢呋喃络合物 、 双氧水 、 pyridinium chlorochromate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.25h， 生成 (R,S)-(4l,5u)-1,2,3,4-tetrahydro-2,2,4-trimethyl-5-(3-trifluoromethylphenyl)-5H-chromeno<3,4-f>quinolin-3-one
  参考文献：
  名称：

  5-Aryl-1,2,3,4-tetrahydrochromeno[3,4-f]quinolin-3-ones as a Novel Class of Nonsteroidal Progesterone Receptor Agonists:  Effect of A-Ring Modification

  摘要：

  Optimization of the 1,2-dihydroquinoline A-ring of a nonsteroidal human progesterone receptor (hPR) agonist pharmacophore (1) was performed by using the cotransfection and receptor binding assays as guides. The S-keto group was discovered to regain the patent agonist activity which was lost upon removal of the 3,4-olefin, and it led to a novel hPR agonist series, 5-aryl-1,2,3,4-tetrahydrochromeno[3,4-f]quinolin-3-ones. The new progestins demonstrated potent hPR agonist activity in the cotransfection assay and high binding affinity similar to progesterone. T47D human breast cancer cell line was employed for further characterization of the new progestins and a number of reference analogues. It was found that the new 3-keto analogues showed full agonist activity in the T47D assay, while the reference compounds from other related nonsteroidal hPR agonist series exhibited only partial agonist activity.

  DOI：

  10.1021/jm980723h
• 作为产物：
  描述：

  8-nitro-6H-benzo[c]chromen-6-one 在 palladium on activated charcoal 正丁基锂 、 氢气 、 碘 作用下， 以 乙酸乙酯 为溶剂， 反应 48.0h， 生成 1,2-Dihydro-2,2,4-trimethyl-5-[3-(trifluoromethyl)phenyl]-5H-chromeno[3,4-f]quinoline
  参考文献：
  名称：

  5-芳基-1,2-二氢色素[3,4-f]喹啉：一类新的非甾体类人孕激素受体激动剂。

  摘要：

  描述了新型非甾体类人孕激素受体（hPR）激动剂5-芳基-1,2-二氢-5H-chromeno [3,4-f]喹啉2的开发。将5-芳基基团引入1,2-二氢香豆素[3,4-f]喹啉核心1是促孕活动的关键。对5-芳基取代基的结构活性关系（SAR）研究产生了一系列有效的hPR激动剂，它们在细胞内显示出与天然激素孕酮（EC50 = 2.9 nM）类似的生物学活性（EC50 = 8-30 nM）。效率范围从28％到96％的检测。大多数类似物表现出与孕酮（Ki = 3.5 nM）相似或更高的结合亲和力（Ki = 0.41-3.6 nM）。三个代表性的类似物（13、15和24）在去卵巢大鼠的乳腺形态/子宫湿重测定中显示了体内活性。

  DOI：

  10.1021/jm9705768

文献信息

• Steroid receptor modulator compounds and methods
  申请人：LIGAND PHARMACEUTICALS INCORPORATED

  公开号：EP1041066A1

  公开（公告）日：2000-10-04

  Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.

  本发明公开了对类固醇受体具有高亲和力、高选择性调节作用的非类固醇化合物。还公开了含有此类化合物的药物组合物、使用所公开化合物和组合物治疗需要类固醇受体激动剂或拮抗剂治疗的患者的方法、制备化合物时有用的中间体以及制备类固醇受体调节剂化合物的工艺。
• 5-Aryl-1,2,3,4-tetrahydrochromeno[3,4-<i>f</i>]quinolin-3-ones as a Novel Class of Nonsteroidal Progesterone Receptor Agonists:  Effect of A-Ring Modification
  作者：Lin Zhi、Christopher M. Tegley、Keith B. Marschke、Dale E. Mais、Todd K. Jones

  DOI：10.1021/jm980723h

  日期：1999.4.22

  Optimization of the 1,2-dihydroquinoline A-ring of a nonsteroidal human progesterone receptor (hPR) agonist pharmacophore (1) was performed by using the cotransfection and receptor binding assays as guides. The S-keto group was discovered to regain the patent agonist activity which was lost upon removal of the 3,4-olefin, and it led to a novel hPR agonist series, 5-aryl-1,2,3,4-tetrahydrochromeno[3,4-f]quinolin-3-ones. The new progestins demonstrated potent hPR agonist activity in the cotransfection assay and high binding affinity similar to progesterone. T47D human breast cancer cell line was employed for further characterization of the new progestins and a number of reference analogues. It was found that the new 3-keto analogues showed full agonist activity in the T47D assay, while the reference compounds from other related nonsteroidal hPR agonist series exhibited only partial agonist activity.
• 5-Aryl-1,2-dihydrochromeno[3,4-<i>f</i>]quinolines:  A Novel Class of Nonsteroidal Human Progesterone Receptor Agonists
  作者：Lin Zhi、Christopher M. Tegley、E. Adam Kallel、Keith B. Marschke、Dale E. Mais、Marco M. Gottardis、Todd K. Jones

  DOI：10.1021/jm9705768

  日期：1998.1.1

  The development of a novel class of nonsteroidal human progesterone receptor (hPR) agonists, 5-aryl-1,2-dihydro-5H-chromeno[3,4-f]quinolines 2, is described. The introduction of a 5-aryl group into the 1,2-dihydrocoumarino[3,4-f]quinoline core 1 is the key for progestational activities. The structure-activity relationship (SAR) studies of the 5-aryl substituents generated a series of potent hPR agonists

  描述了新型非甾体类人孕激素受体（hPR）激动剂5-芳基-1,2-二氢-5H-chromeno [3,4-f]喹啉2的开发。将5-芳基基团引入1,2-二氢香豆素[3,4-f]喹啉核心1是促孕活动的关键。对5-芳基取代基的结构活性关系（SAR）研究产生了一系列有效的hPR激动剂，它们在细胞内显示出与天然激素孕酮（EC50 = 2.9 nM）类似的生物学活性（EC50 = 8-30 nM）。效率范围从28％到96％的检测。大多数类似物表现出与孕酮（Ki = 3.5 nM）相似或更高的结合亲和力（Ki = 0.41-3.6 nM）。三个代表性的类似物（13、15和24）在去卵巢大鼠的乳腺形态/子宫湿重测定中显示了体内活性。