N-(cyclopropylmethyl)-10-[4-(1,1-difluoroethyl)phenyl]sulfonyl-5-thia-1,8,11,12-tetrazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaen-7-amine | 1436388-63-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: N-(cyclopropylmethyl)-10-[4-(1,1-difluoroethyl)phenyl]sulfonyl-5-thia-1,8,11,12-tetrazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaen-7-amine
• CAS: 1436388-63-4
• 化学式: C₁₉H₁₇F₂N₅O₂S₂
• 分子量: 449.505
• InChiKey: HZAAYXYYNNTFLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-((4-(1,1-difluoroethyl)phenyl)sulfonyl)thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidin-5(4H)-one 、 环丙基甲胺 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 0.5h， 以80%的产率得到N-(cyclopropylmethyl)-10-[4-(1,1-difluoroethyl)phenyl]sulfonyl-5-thia-1,8,11,12-tetrazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaen-7-amine
  参考文献：
  名称：

  1,1-Difluoroethyl-substituted triazolothienopyrimidines as inhibitors of a human urea transport protein (UT-B): New analogs and binding model

  摘要：

  The kidney urea transport protein UT-B is an attractive target for the development of small-molecule inhibitors with a novel diuretic ('urearetic') action. Previously, two compounds in the triazolothienopyrimidine scaffold (1a and 1c) were reported as UT-B inhibitors. Compound 1c incorporates a 1,1-difluoroethyl group, which affords improved microsomal stability when compared to the corresponding ethyl-substituted compound 1a. Here, a small focused library (4a-4f) was developed around lead inhibitor 1c to investigate the requirement of an amidine-linked thiophene in the inhibitor scaffold. Two compounds (4a and 4b) with nanomolar inhibitory potency (IC50 approximate to 40 nM) were synthesized. Computational docking of lead structure 1c and 4a-4f into a homology model of the UT-B cytoplasmic surface suggested binding with the core heterocycle buried deep into the hydrophobic pore region of the protein. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.089