(E)-ethyl 2-methyl-4-(9-(2-methyl-1H-indol-3-yl)-7-nitro-2,3,4,4a,9,9a-hexahydro-1H-xanthen-4a-yl)but-2-enoate | 1612138-67-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (E)-ethyl 2-methyl-4-(9-(2-methyl-1H-indol-3-yl)-7-nitro-2,3,4,4a,9,9a-hexahydro-1H-xanthen-4a-yl)but-2-enoate
• CAS: 1612138-67-6
• 化学式: C₂₉H₃₂N₂O₅
• 分子量: 488.583
• InChiKey: HZHKFTNMJCSMMB-NBVRZTHBSA-N

物化性质

• 沸点：
  636.8±55.0 °C(predicted)
• 密度：
  1.234±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.74
• 重原子数：
  36.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  94.46
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (E)-ethyl 2-methyl-4-(9-(2-methyl-1H-indol-3-yl)-7-nitro-2,3,4,4a,9,9a-hexahydro-1H-xanthen-4a-yl)but-2-enoate 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.5h， 以60.5%的产率得到(E)-2-methyl-4-(9-(2-methyl-1H-indol-3-yl)-7-nitro-2,3,4,4a,9,9a-hexahydro-1H-xanthen-4a-yl)but-2-enoic acid
  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：

  3-(4a-allyl-7-nitro-2,3,4,4a,9,9a-hexahydro-1H-xanthen-9-yl)-2-methyl-1H-indole 在 4-二甲氨基吡啶 、 臭氧 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 6.83h， 生成 (E)-ethyl 2-methyl-4-(9-(2-methyl-1H-indol-3-yl)-7-nitro-2,3,4,4a,9,9a-hexahydro-1H-xanthen-4a-yl)but-2-enoate
  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