2,5-dihydro-9-methoxy-5-oxo-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline | 179896-45-8

• 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: 2,5-dihydro-9-methoxy-5-oxo-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline
• 英文别名: 9-methoxy-2,2,4-trimethyl-1H-chromeno[3,4-f]quinolin-5-one
• CAS: 179896-45-8
• 化学式: C₂₀H₁₉NO₃
• 分子量: 321.376
• InChiKey: DPYXRYJBFGKZTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,5-dihydro-9-methoxy-5-oxo-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinoline 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 生成 1,2-dihydro-5-hydroxy-9-methoxy-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-Methoxy-8-nitro-benzo[c]chromen-6-one 在 碘 、 tin(ll) chloride 作用下， 以 乙酸乙酯 为溶剂， 反应 20.0h， 生成 2,5-dihydro-9-methoxy-5-oxo-2,2,4-trimethyl-1H-[1]benzopyrano[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

文献信息

• Synthesis and Characterization of Non-Steroidal Ligands for the Glucocorticoid Receptor:  Selective Quinoline Derivatives with Prednisolone-Equivalent Functional Activity
  作者：Michael J. Coghlan、Philip R. Kym、Steven W. Elmore、Alan X. Wang、Jay R. Luly、Denise Wilcox、Michael Stashko、Chun-Wei Lin、Jeffrey Miner、Curtis Tyree、Masaki Nakane、Peer Jacobson、Benjamin C. Lane

  DOI：10.1021/jm010228c

  日期：2001.8.1

  A novel class of functional ligands for the human glucocorticoid receptor is described. Substituents in the C-10 position of the tetracyclic core are essential for glucocorticoid receptor (GR) selectivity versus other steroid receptors. The C-5 position is derivatized with meta-substituted aromatic groups, resulting in analogues with a high affinity for GR (K-i = 2.4-9.3 nM) and functional activity comparable to prednisolone in reporter gene assays of glucocorticoid-mediated gene transcription. The biological activity of these novel quinolines was also prednisolone-equivalent in whole cell assays of glucocorticoid function, and compound 13 was similar to prednisolone (po ED50 = 2.8 mpk for 13 vs ED50 = 1.2 mpk for prednisolone) in a rodent model of asthma (sephadex-induced eosinophil influx).
• 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.
• 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.