4-(3'-ethoxybiphenyl-4-yl)-3,6-dimethyl-1-(2-methylphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3'-ethoxybiphenyl-4-yl)-3,6-dimethyl-1-(2-methylphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one
• 英文别名: (4R,6S)-4-[4-(3-ethoxyphenyl)phenyl]-3,6-dimethyl-1-(2-methylphenyl)-4,8-dihydropyrazolo[3,4-e][1,4]thiazepin-7-one
• 化学式: C₂₉H₂₉N₃O₂S
• 分子量: 483.634
• InChiKey: XKKBLDVDKBZTQT-CCLHPLFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (2-甲基苯基)肼 在 盐酸 作用下， 以 水 、 甲苯 为溶剂， 反应 24.0h， 生成 4-(3'-ethoxybiphenyl-4-yl)-3,6-dimethyl-1-(2-methylphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one 、 4-(3'-ethoxybiphenyl-4-yl)-3,6-dimethyl-1-(2-methylphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one
  参考文献：
  名称：

  Pyrazole[3,4-e][1,4]thiazepin-7-one derivatives as a novel class of Farnesoid X Receptor (FXR) agonists

  摘要：

  A virtual screening procedure was applied to the discovery of structurally diverse non-steroidal Farnesoid X Receptor (FXR) agonists. From 117 compounds selected by virtual screening, a total of 47 compounds were found to be FXR agonists, with 34 of them showing activity below a concentration of 20 mu M. 1H-Pyrazole[3,4-e][1,4]thiazepin-7-one-based hit compound 7 was chosen for hit-to-lead optimization. A large number of 1H-pyrazole[3,4-e][1,4]thiazepin-7-one derivatives was designed, synthesized, and evaluated by a cell-based luciferase transactivation assay for their agonistic activity against FXR. Most of them exhibited low micromolar range of potency and very high efficacy. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.021