4-(4-chloro-3-nitro-phenyl)-morpholine | 28340-70-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 4-(4-chloro-3-nitro-phenyl)-morpholine
• 英文别名: 4-(4-chloro-3-nitrophenyl)morpholine；4-Morpholino-2-nitro-chlorbenzol；4-Morpholino-2-nitrochlorbenzol；4-{4-Chloro-3-nitrophenyl}morpholine
• CAS: 28340-70-7
• 化学式: C₁₀H₁₁ClN₂O₃
• 分子量: 242.662
• InChiKey: QLMARGYNEQASGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  58.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-chloro-3-nitro-phenyl)-morpholine 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 生成
  参考文献：
  名称：

  Identification and Optimization of Benzimidazole Sulfonamides as Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists with in Vivo Activity

  摘要：

  We report here a novel series of benzimidazole sulfonamides that act as antagonists of the S1P(1) receptor, identified by exploiting an understanding of the pharmacophore of a high throughput screening (HTS)-derived series of compounds described previously. Lead compound 2 potently inhibits SIP-induced receptor internalization in a cell-based assay (EC50 = 0.05 mu M), but has poor physical properties and metabolic stability. Evolution of this compound through structure-activity relationship development and property optimization led to in vivo probes such as 4. However, this compound was unexpectedly found to be a potent CYP3A inducer in human hepatocytes, and thus further chemistry efforts were directed at addressing this liability. By employing a pregnane X receptor (PXR) reporter gene assay to prioritize compounds for further testing in human hepatocytes, we identified lipophilicity as a key molecular property influencing the likelihood of P450 induction. Ultimately, we have identified compounds such as 46 and 47, which demonstrate the desired S1P(1) antagonist activity while having greatly reduced risk of CYP3A induction in humans. These compounds have excellent oral bioavailability in preclinical species and exhibit pharmacodynamic effects of S1P(1) antagonism in several in vivo models following oral dosing. Relatively modest antitumor activity was observed in multiple xenograft models, however, suggesting that selective S1P(1) antagonists would have limited utility as anticancer therapeutics as single agents.

  DOI：

  10.1021/acs.jmedchem.5b01078
• 作为产物：
  描述：

  2,2'-二溴二乙醚 、 3-硝基-4-氯苯胺 在 potassium carbonate 作用下， 以 乙二醇二甲醚 为溶剂， 反应 48.0h， 以23%的产率得到4-(4-chloro-3-nitro-phenyl)-morpholine
  参考文献：
  名称：

  WO2006/127458

  摘要：

  公开号：

文献信息

• NOVEL CHEMICAL COMPOUNDS
  申请人：Duffy Kevin

  公开号：US20090203692A1

  公开（公告）日：2009-08-13

  This invention relates to newly identified compounds for inhibiting hYAK3 proteins and methods for treating diseases associated with hYAK3 activity.

  本发明涉及新鉴定的化合物，用于抑制hYAK3蛋白质，并用于治疗与hYAK3活性相关的疾病的方法。
• [EN] NOVEL CHEMICAL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES CHIMIQUES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2006127458A2

  公开（公告）日：2006-11-30

  [EN] This invention relates to newly identified compounds for inhibiting hYAK3 proteins and methods for treating diseases associated with hYAK3 activity.
  [FR] La présente invention concerne des composés récemment identifiés qui permettent d'inhiber les protéines hYAK3, ainsi que des méthodes de traitement de maladies associées à l'activité hYAK3.