8-fluoro-2,2,4-trimethyl-1H-chromeno[3,4-f]quinolin-5-one | 179895-42-2

• 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: 8-fluoro-2,2,4-trimethyl-1H-chromeno[3,4-f]quinolin-5-one
• CAS: 179895-42-2
• 化学式: C₁₉H₁₆FNO₂
• 分子量: 309.34
• InChiKey: IJKZWLDNBQOSJD-UHFFFAOYSA-N

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：

  8-fluoro-2,2,4-trimethyl-1H-chromeno[3,4-f]quinolin-5-one 在 二异丁基氢化铝 、 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 生成 8-Fluoro-5-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-6-oxa-1-aza-chrysene
  参考文献：
  名称：

  5-Alkyl 1,2-dihydrochromeno[3,4-f]quinolines: a novel class of nonsteroidal progesterone receptor modulators

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(98)00608-8
• 作为产物：
  描述：

  2-溴-5-硝基苯甲酸 在 palladium on activated charcoal 四(三苯基膦)钯 、 三氯化铝 、 氯化亚砜 、 氢气 、 碘 、 sodium carbonate 、 溶剂黄146 作用下， 以 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 反应 51.67h， 生成 8-fluoro-2,2,4-trimethyl-1H-chromeno[3,4-f]quinolin-5-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

• 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。
• US8017775B2
  申请人：——

  公开号：US8017775B2

  公开（公告）日：2011-09-13
• US8420635B2
  申请人：——

  公开号：US8420635B2

  公开（公告）日：2013-04-16