(3,5-dibromo-2-hydroxyphenyl)dimorpholinomethane | 239438-66-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (3,5-dibromo-2-hydroxyphenyl)dimorpholinomethane
• 英文别名: 2,4-Dibromo-6-(dimorpholin-4-ylmethyl)phenol
• CAS: 239438-66-5
• 化学式: C₁₅H₂₀Br₂N₂O₃
• 分子量: 436.143
• InChiKey: WPSUHYFMDUOCKJ-UHFFFAOYSA-N

物化性质

• 沸点：
  457.7±45.0 °C(Predicted)
• 密度：
  1.680±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3,5-dibromo-2-hydroxyphenyl)dimorpholinomethane 反应 0.05h， 生成 4-(5,7-dibromo-9-(2-methyl-1H-indol-3-yl)-2,3,4,4a,9,9a-hexahydro-1H-xanthen-4a-yl)morpholine
  参考文献：
  名称：

  The hit-to-lead optimization of 1,2,3,4,4a,9a-hexahydro-1H-xanthenes as glucocorticoid receptor antagonists

  摘要：

  The structure activity relationship (SAR) study of a 1,2,3,4,4a,9a-hexahydro-1H-xanthene series of selective, human glucocorticoid receptor alpha (hGR alpha) antagonists is reported. Compounds were screened using hydroxyapatite-based GR binding and MMTV-Luc co-transfection reporter gene assays. Four different regions of the scaffold were modified to assess the effects on hGRa antagonism and related potency. Compound 8d exhibits an 8-fold better bioactivity than the original hit 1a, as well as an improved chemical stability, which make it a promising lead for the subsequent optimization. (C) 2014 Ming-Wei Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  DOI：

  10.1016/j.cclet.2014.03.017
• 作为产物：
  描述：

  吗啉 、 3,5-二溴水杨醛 以 异丙醇 为溶剂， 反应 8.0h， 生成 (3,5-dibromo-2-hydroxyphenyl)dimorpholinomethane
  参考文献：
  名称：

  The hit-to-lead optimization of 1,2,3,4,4a,9a-hexahydro-1H-xanthenes as glucocorticoid receptor antagonists

  摘要：

  The structure activity relationship (SAR) study of a 1,2,3,4,4a,9a-hexahydro-1H-xanthene series of selective, human glucocorticoid receptor alpha (hGR alpha) antagonists is reported. Compounds were screened using hydroxyapatite-based GR binding and MMTV-Luc co-transfection reporter gene assays. Four different regions of the scaffold were modified to assess the effects on hGRa antagonism and related potency. Compound 8d exhibits an 8-fold better bioactivity than the original hit 1a, as well as an improved chemical stability, which make it a promising lead for the subsequent optimization. (C) 2014 Ming-Wei Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  DOI：

  10.1016/j.cclet.2014.03.017

文献信息

• Synthesis of hexa-, tetra-, and dihydroxanthene derivatives from salicylaldehyde aminals
  作者：L. Yu. Ukhin、V. A. Kharlanov、E. V. Solomovich、O. V. Shishkin

  DOI：10.1007/bf02494643

  日期：1999.5

  Salicylaldehyde aminals react with cyclohexanone upon heating to form tetrahydroxanthene derivatives. The structure of one of these derivatives,viz., 5,7-dichloro-4a-morpholino-1,2,3,4-tetrahydro-4aH-xanthene, was established by X-ray diffraction analysis. The scheme of the reaction was suggested, which involves cycloaddition of intermediateo-methylenequinone (from aminal) and enamine (from cyclohexanone)

  水杨醛缩醛胺在加热时与环己酮反应形成四氢氧杂蒽衍生物。这些衍生物之一的结构，即 5,7-dichloro-4a-morpholino-1,2,3,4-tetrahydro-4aH-xanthene，通过 X 射线衍射分析确定。建议的反应方案包括中间体-亚甲基醌（来自胺醛）和烯胺（来自环己酮）的环加成。水杨醛缩醛胺与由环己酮形成的烯胺反应可以依次得到六氢氧杂蒽、四氢氧杂蒽和二氢氧杂蒽的衍生物。开发了合成这些化合物的程序。 N-取代的 4a-氨基-7-硝基-1,2,3,4-四氢-4aH-呫吨也通过二烷基铵 2-甲酰基-4-硝基苯氧化物与上述烯胺。
• ——
  作者：L. Yu. Ukhin、L. V. Belousova、Zh. I. Orlova、M. S. Korobov、G. S. Borodkin

  DOI：10.1023/a:1021721211363

  日期：——
• ——
  作者：L. Yu. Ukhin、L. V. Belousova、Zh. I. Orlova、S. V. Shishkina、O. V. Shishkin

  DOI：10.1023/a:1020956614588

  日期：——

  The reactions of aminals, the Mannich bases, and azomethines derived from substituted salicylaldehydes were studied. Derivatives of tetrahydrocyclopenta[b]- and hexahydro-cyclohepta[b]chromenes and substituted 2,2'-spirobichromenes were prepared from aminals, and substituted hexahydroxanthenes were synthesized from the Mannich bases. Azomethine derivatives of 5-nitrosalicylaldehyde and aliphatic amines react with cyclohexanone to form 4a-amino-7-nitro-2,3,4,4a-tetrahydro-1H-xanthenes. 4a-Morpholino-7-nitro-9-phenylethynyl-1,2,3,4,9,9a-hexahydroxanthene was studied by X-ray diffraction analysis.
• ——
  作者：L. Yu. Ukhin

  DOI：10.1023/a:1023923226389

  日期：——

  Fusion of 2-methylindole with morphinals of substituted salicylaldehydes (in a ratio of 1 : 1) afforded 3-[(2-hydroxyaryl)morpholinomethyl]-2-methylindoles as normal products of the Mannich reaction. In some cases, the reactions with an excess of 2-methylindole resulted in unusual condensation accompanied by the replacement of the OH group by the morpholino group to form bis(2-methylindol-3-yl)(2-morpholinoaryl)methanes.
• The hit-to-lead optimization of 1,2,3,4,4a,9a-hexahydro-1H-xanthenes as glucocorticoid receptor antagonists
  作者：Yan-Hui Zhu、Meng Zhang、Qun-Yi Li、Qing Liu、Jie Zhang、Yun-Yun Yuan、Fa-Jun Nan、Ming-Wei Wang

  DOI：10.1016/j.cclet.2014.03.017

  日期：2014.5

  The structure activity relationship (SAR) study of a 1,2,3,4,4a,9a-hexahydro-1H-xanthene series of selective, human glucocorticoid receptor alpha (hGR alpha) antagonists is reported. Compounds were screened using hydroxyapatite-based GR binding and MMTV-Luc co-transfection reporter gene assays. Four different regions of the scaffold were modified to assess the effects on hGRa antagonism and related potency. Compound 8d exhibits an 8-fold better bioactivity than the original hit 1a, as well as an improved chemical stability, which make it a promising lead for the subsequent optimization. (C) 2014 Ming-Wei Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.