1-((5-(((2-(diethylamino)ethyl)(methyl)amino)methyl)-1-((4'-(trifluoromethyl)biphenyl-4-yl)methyl)-1H-imidazol-2-yl)methyl)-2-thioxo-2,3,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-4(5H)-one | 1432488-15-7

• 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: 1-((5-(((2-(diethylamino)ethyl)(methyl)amino)methyl)-1-((4'-(trifluoromethyl)biphenyl-4-yl)methyl)-1H-imidazol-2-yl)methyl)-2-thioxo-2,3,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-4(5H)-one
• CAS: 1432488-15-7
• 化学式: C₃₄H₄₄F₃N₅O₂
• 分子量: 611.751
• InChiKey: TXPATRYUWVGKFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.48
• 重原子数：
  44.0
• 可旋转键数：
  15.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  62.63
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1-((5-(((2-(diethylamino)ethyl)(methyl)amino)methyl)-1-((4'-(trifluoromethyl)biphenyl-4-yl)methyl)-1H-imidazol-2-yl)methyl)-2-thioxo-2,3,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-4(5H)-one 在 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.0h， 生成 2-(4-fluorobenzylthio)-1-((5-((methyl(2-(piperidin-1-yl)ethyl)amino)methyl)-1-((4'-(trifluoromethyl)biphenyl-4-yl)methyl)-1H-imidazol-2-yl)methyl)-6,7-dihydro-1H-cyclopenta[d]pyrimidin-4(5H)-one
  参考文献：
  名称：

  Triazole derivatives: A series of Darapladib analogues as orally active Lp-PLA2 inhibitors

  摘要：

  This Letter reports our efforts towards the optimization of our previously identified series of imidazole and triazole derivatives that lead to the discovery of a series of orally active Lp-PLA(2) inhibitors in C57 mice. These inhibitors are characterized by the presence of a diamine side chain in the molecules, such as 2c, 2f, and 4a. The introduction of the terminal-end amine succeeded in maintaining the in vitro activities at sub-nanomolar levels. The vivo activities could be greatly affected by variations in the two amines via modulating the metabolic stability and lipophilicity of the compounds. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.062
• 作为产物：
  描述：

  [3-(4-溴苄基)-3H-咪唑-4-基]甲醇 在 manganese(IV) oxide 、 四(三苯基膦)钯 、 硅酸四乙酯 、 palladium 10% on activated carbon 、 二苯基膦叠氮化物 、 氢气 、 三乙酰氧基硼氢化钠 、 caesium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 20.0~60.0 ℃ 、101.33 kPa 条件下， 反应 59.0h， 生成 1-((5-(((2-(diethylamino)ethyl)(methyl)amino)methyl)-1-((4'-(trifluoromethyl)biphenyl-4-yl)methyl)-1H-imidazol-2-yl)methyl)-2-thioxo-2,3,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-4(5H)-one
  参考文献：
  名称：

  Triazole derivatives: A series of Darapladib analogues as orally active Lp-PLA2 inhibitors

  摘要：

  This Letter reports our efforts towards the optimization of our previously identified series of imidazole and triazole derivatives that lead to the discovery of a series of orally active Lp-PLA(2) inhibitors in C57 mice. These inhibitors are characterized by the presence of a diamine side chain in the molecules, such as 2c, 2f, and 4a. The introduction of the terminal-end amine succeeded in maintaining the in vitro activities at sub-nanomolar levels. The vivo activities could be greatly affected by variations in the two amines via modulating the metabolic stability and lipophilicity of the compounds. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.062