2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-propyl-1H-[1]benzopyrano[3,4-f]quinoline

• 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: 2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-propyl-1H-[1]benzopyrano[3,4-f]quinoline
• 英文别名: 10-Methoxy-2,2,4-trimethyl-5-propyl-2,5-dihydro-1H-6-oxa-1-aza-chrysene；10-methoxy-2,2,4-trimethyl-5-propyl-1,5-dihydrochromeno[3,4-f]quinoline
• 化学式: C₂₃H₂₇NO₂
• 分子量: 349.473
• InChiKey: DWGAKCJFXFNMID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  丙基氯化镁 、 5,10-Dimethoxy-2,2,4-trimethyl-2,5-dihydro-1H-6-oxa-1-aza-chrysene 在 三氟化硼乙醚 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.25h， 以55%的产率得到2,5-dihydro-10-methoxy-2,2,4-trimethyl-5-propyl-1H-[1]benzopyrano[3,4-f]quinoline
  参考文献：
  名称：

  Nonsteroidal Selective Glucocorticoid Modulators:  the Effect of C-5 Alkyl Substitution on the Transcriptional Activation/Repression Profile of 2,5-Dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines

  摘要：

  The preparation and characterization of a series of selective glucocorticoid receptor modulators are described. The preliminary structure-activity relationship of nonaromatic C-5 substitution on the tetracyclic quinoline core showed a preference for small lipophilic side chains. Proper substitution at this position maintained the transcriptional repression of proinflammatory transcription factors while diminishing the transcriptional activation activity of the ligand/glucocorticoid receptor complex. The optimal compounds described in this study were the allyl analogue 18 and cyclopentyl analogue 32. These candidates showed slightly less potent, highly efficacious E-selectin repression with significantly reduced levels of glucocorticoid response element activation in reporter gene assays vs prednisolone. Allyl analogue 18 was evaluated in vivo. An oral dose of 18 showed an ED50 = 1.7 mg/kg as compared to 1.2 mg/kg for prednisolone in the Sephadex-induced pulmonary eosinophilia model and an ED50 = 15 mg/kg vs 4 mg/kg for prednisolone in the carrageenan-induced paw edema model.

  DOI：

  10.1021/jm010367u

文献信息

• Glucocortiocoid-selective antinflammatory agents
  申请人：Abbott Laboratories and Ligand Pharmaceuticals Incorporated

  公开号：US20030073703A1

  公开（公告）日：2003-04-17

  Compounds having Formula I 1 are useful for partially or fully antagonizing, repressing, agonizing, or modulating the glucocorticoid receptor and treating immune, autoimmune and inflammatory diseases in a mammal. Also disclosed are pharmaceutical compositions comprising compounds of Formula I and methods of inhibiting immune or autoimmune diseases in a mammal.

  具有I1式的化合物对于部分或完全对抗、抑制、激动或调节糖皮质激素受体，并治疗哺乳动物的免疫、自身免疫和炎症性疾病是有用的。此外，还揭示了包含I式化合物的制药组合物和抑制哺乳动物的免疫或自身免疫疾病的方法。
• Androgen Receptor Modulator Compounds and Methods
  申请人：Loren Jon C.

  公开号：US20090227571A1

  公开（公告）日：2009-09-10

  Provided herein are compounds that bind to androgen receptors and modulate the activity and/or the amount of androgen receptors and to methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.

  本文提供了一些结合雄激素受体并调节雄激素受体的活性和/或数量的化合物，以及制备和使用这些化合物的方法。还提供了包括这些化合物的组合物以及制备和使用这些组合物的方法。
• GLUCOCORTICOID-SELECTIVE ANTI-INFLAMMATORY AGENTS
  申请人：ABBOTT LABORATORIES

  公开号：EP1053239B1

  公开（公告）日：2003-01-08
• GLUCOCORTIOCOID-SELECTIVE ANTIINFLAMMATORY AGENTS
  申请人：Abbott Laboratories

  公开号：EP1299392A2

  公开（公告）日：2003-04-09
• US6506766B1
  申请人：——

  公开号：US6506766B1

  公开（公告）日：2003-01-14