9-fluoro-2,2,4-trimethyl-1H-chromeno[3,4-f]quinolin-5-one | 179895-41-1

• 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: 9-fluoro-2,2,4-trimethyl-1H-chromeno[3,4-f]quinolin-5-one
• CAS: 179895-41-1
• 化学式: C₁₉H₁₆FNO₂
• 分子量: 309.34
• InChiKey: SPEXHWMWAJGSOP-UHFFFAOYSA-N

物化性质

• 沸点：
  487.7±45.0 °C(Predicted)
• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-fluoro-2,2,4-trimethyl-1H-chromeno[3,4-f]quinolin-5-one 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 生成 9-fluoro-1,2-dihydro-5-hydroxy-2,2,4-trimethyl-5H-chromeno[3,4-f]quinoline
  参考文献：
  名称：

  Development of progesterone receptor antagonists from 1,2-dihydrochromeno[3,4-f]quinoline agonist pharmacophore

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(03)00256-7
• 作为产物：
  描述：

  2-Fluoro-8-nitrobenzo[c]chromen-6-one 在 碘 、 calcium chloride 、 锌 作用下， 以 乙醇 为溶剂， 反应 53.0h， 生成 9-fluoro-2,2,4-trimethyl-1H-chromeno[3,4-f]quinolin-5-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

文献信息

• 5-Benzylidene-1,2-dihydrochromeno[3,4-<i>f</i>]quinolines as Selective Progesterone Receptor Modulators
  作者：Lin Zhi、Christopher M. Tegley、Barbara Pio、James P. Edwards、Mehrnouch Motamedi、Todd K. Jones、Keith B. Marschke、Dale E. Mais、Boris Risek、William T. Schrader

  DOI：10.1021/jm020477g

  日期：2003.9.1

  4-f]quinolines (4) were synthesized and tested in bioassays to evaluate their progestational activities, receptor- and tissue-selectivity profiles as selective progesterone receptor modulators (SPRMs). Most of the new analogues exhibited as highly potent progestins with more than 100-fold receptor selectivity over other steroid hormone receptors and LG120920 (7b) demonstrated tissue selectivity toward uterus

  合成了一系列5-beneidene-1,2-dihydrochromeno [3,4-f]喹啉（4），并在生物测定法中进行了测试，以评估其作为选择性孕激素受体调节剂（SPRM）的孕激素活性，受体和组织选择性。 。在啮齿动物模型中，口服给药后，大多数新类似物表现为高效的孕激素，其受体选择性是其他类固醇激素受体的100倍以上，而LG120920（7b）表现出对子宫和阴道的组织选择性。
• Novel 1-2-Dihydroquinoline Derivative Having Glucocorticoid Receptor Binding Activity
  申请人：Matsuda Mamoru

  公开号：US20090326009A1

  公开（公告）日：2009-12-31

  An object of the present invention is to study synthesis of a novel 1,2-dihydroquinoline derivative and to find a pharmacological action of the derivative. A compound represented by the general formula (1) or a salt thereof is effective in the treatment of a glucocorticoid receptor-related disease. In the formula, the ring X represents a benzene ring or a pyridine ring; R 1 represents a halogen atom, an alkyl group, a hydroxy group, an alkoxy group, an amino group or the like; p represents an integer of 0 to 5; R 2 represents a halogen atom, an alkyl group, a hydroxy group or the like; q represents an integer of 0 to 2; R 3 represents a hydrogen atom, an alkyl group, an alkenyl group or the like; R 4 and R 5 represent a hydrogen atom or the like; R 6 represents a hydrogen atom or the like; A represents an alkylene group or the like; and R 7 represents OR 8 , NR 8 R 9 , SR 8 , S(O)R 8 or S(O) 2 R 8 , wherein R 8 represents an aryl group, a heterocyclic group or the like and R 9 represents a hydrogen atom or the like.

  本发明的目的是研究合成一种新型1,2-二氢喹啉衍生物，并发现该衍生物的药理作用。通式（1）表示的化合物或其盐在治疗糖皮质激素受体相关疾病方面具有有效性。在该式中，环X表示苯环或吡啶环；R1表示卤素原子、烷基、羟基、烷氧基、氨基或类似物；p表示0至5的整数；R2表示卤素原子、烷基、羟基或类似物；q表示0至2的整数；R3表示氢原子、烷基、烯基或类似物；R4和R5表示氢原子或类似物；R6表示氢原子或类似物；A表示烷基链或类似物；R7表示OR8、NR8R9、SR8、S（O）R8或S（O）2R8，其中R8表示芳基、杂环基或类似物，R9表示氢原子或类似物。
• Method for preventing or treating a glucocorticoid receptor-related disease
  申请人：Matsuda Mamoru

  公开号：US20110263589A1

  公开（公告）日：2011-10-27

  A method of preventing or treating a glucocorticoid receptor-related disease involving administering a therapeutically effective amount of a 1,2-dihydroquinoline compound or a pharmaceutically acceptable salt thereof.

  一种预防或治疗与糖皮质激素受体相关的疾病的方法，包括给予治疗有效量的1,2-二氢喹啉化合物或其药学上可接受的盐。
• NOVEL 1-2-DIHYDROQUINOLINE DERIVATIVE HAVING GLUCOCORTICOID RECEPTOR BINDING ACTIVITY
  申请人：SANTEN PHARMACEUTICAL CO., LTD.

  公开号：EP1944290A1

  公开（公告）日：2008-07-16

  An object of the present invention is to study synthesis of a novel 1,2-dihydroquinoline derivative and to find a pharmacological action of the derivative. A compound represented by the general formula (1) or a salt thereof is effective in the treatment of a glucocorticoid receptor-related disease. In the formula, the ring X represents a benzene ring or a pyridine ring; R1 represents a halogen atom, an alkyl group, a hydroxy group, an alkoxy group, an amino group or the like; p represents an integer of 0 to 5; R2 represents a halogen atom, an alkyl group, a hydroxy group or the like; q represents an integer of 0 to 2; R3 represents a hydrogen atom, an alkyl group, an alkenyl group or the like; R4 and R5 represent a hydrogen atom or the like; R6 represents a hydrogen atom or the like; A represents an alkylene group or the like; and R7 represents OR8, NR8R9, SR8, S (O) R8 or S (O)2R8, wherein R8 represents an aryl group, a heterocyclic group or the like and R9 represents a hydrogen atom or the like.

  本发明的目的是研究一种新型 1,2-二氢喹啉衍生物的合成，并找到该衍生物的药理作用。通式（1）代表的化合物或其盐可有效治疗糖皮质激素受体相关疾病。式中，环 X 代表苯环或吡啶环；R1 代表卤素原子、烷基、羟基、烷氧基、氨基或类似基团；p 代表 0 至 5 的整数；R2 代表卤素原子、烷基、羟基或类似基团；q 代表 0 至 2 的整数；R3 代表氢原子、烷基、烯基或类似物； R4 和 R5 代表氢原子或类似物； R6 代表氢原子或类似物； A 代表亚烷基或类似物；以及 R7 代表 OR8、NR8R9、SR8、S (O) R8 或 S (O)2R8 其中 R8 代表芳基、杂环基或类似物，R9 代表氢原子或类似物。
• 5-Alkyl 1,2-dihydrochromeno[3,4-f]quinolines: a novel class of nonsteroidal progesterone receptor modulators
  作者：Lin Zhi、Christopher M Tegley、James P Edwards、Sarah J West、Keith B Marschke、Marco M Gottardis、Dale E Mais、Todd K Jones

  DOI：10.1016/s0960-894x(98)00608-8

  日期：1998.12

  A series of nonsteroidal human progesterone receptor (hPR) agonists, 5-alkyl 1,2-dihydrochromeno[3,4-f]quinolines, was synthesized and evaluated in cotransfection and competitive receptor binding assays. The 5-alkyl substitution was shown to be responsible for the agonist activity and substitution at C9 dramatically enhanced the potency. A number of analogues in this series showed activities similar to or better than progesterone in the cotransfection and binding assays and analogue 15 exhibited similar in vivo activity as medroxyprogesterone acetate (MPA) in murine uterine wet weight/mammary gland morphology assays. (C) 1998 Elsevier Science Ltd. All rights reserved.