methyl 2-((4-bromo-2-cyano-5-(3-((3,3,5,5-tetramethylcyclohexyl)amino)phenyl)thiophen-3-yl)oxy)acetate | 942942-18-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl 2-((4-bromo-2-cyano-5-(3-((3,3,5,5-tetramethylcyclohexyl)amino)phenyl)thiophen-3-yl)oxy)acetate
• CAS: 942942-18-9
• 化学式: C₂₄H₂₉BrN₂O₃S
• 分子量: 505.476
• InChiKey: QETCPYNBHQQUIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.62
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  71.35
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl 2-((4-bromo-2-cyano-5-(3-((3,3,5,5-tetramethylcyclohexyl)amino)phenyl)thiophen-3-yl)oxy)acetate 在 sodium azide 、 水 、 zinc dibromide 作用下， 以 异丙醇 为溶剂， 以80%的产率得到2-(4-bromo-5-(3-(3,3,5,5-tetramethylcyclohexylamino)phenyl)-2-(2H-tetrazol-5-yl)thiophen-3-yloxy)acetic acid
  参考文献：
  名称：

  Probing acid replacements of thiophene PTP1B inhibitors

  摘要：

  The following account describes our systematic effort to replace one of the carboxylate groups of our diacid thiophene PTP1B inhibitors. Active hits were validated using enzymatic assays before pursuing efforts to improve the potency. Only when the C2 carboxylic acid was replaced with another ionizable functional group was reversible and competitive inhibition retained. Use of a tetrazole ring or 1,2,5-thiadiazolidine-3-one-1,1-dioxide as a carboxylate mimetic led to the discovery of two unique starting series that showed improved permeability (PAMPA) and potency of the order of 300 nM. The SAR from these efforts underscores some of the major challenges in developing small molecule inhibitors for PTP1B. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.043
• 作为产物：
  描述：

  Methyl 2-(4,5-dibromo-2-carbamoylthiophen-3-yl)oxyacetate 在 四(三苯基膦)钯 potassium fluoride 、 三聚氯氰 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 2-((4-bromo-2-cyano-5-(3-((3,3,5,5-tetramethylcyclohexyl)amino)phenyl)thiophen-3-yl)oxy)acetate
  参考文献：
  名称：

  Probing acid replacements of thiophene PTP1B inhibitors

  摘要：

  The following account describes our systematic effort to replace one of the carboxylate groups of our diacid thiophene PTP1B inhibitors. Active hits were validated using enzymatic assays before pursuing efforts to improve the potency. Only when the C2 carboxylic acid was replaced with another ionizable functional group was reversible and competitive inhibition retained. Use of a tetrazole ring or 1,2,5-thiadiazolidine-3-one-1,1-dioxide as a carboxylate mimetic led to the discovery of two unique starting series that showed improved permeability (PAMPA) and potency of the order of 300 nM. The SAR from these efforts underscores some of the major challenges in developing small molecule inhibitors for PTP1B. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.043