2-((4,5-dibromo-2-(2-(tert-butoxy)acetyl)thiophen-3-yl)oxy)acetic acid | 942941-56-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-((4,5-dibromo-2-(2-(tert-butoxy)acetyl)thiophen-3-yl)oxy)acetic acid
• CAS: 942941-56-2
• 化学式: C₁₂H₁₄Br₂O₅S
• 分子量: 430.114
• InChiKey: QYSLFWWQZBTZNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.73
• 重原子数：
  20.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.83
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-((4,5-dibromo-2-(2-(tert-butoxy)acetyl)thiophen-3-yl)oxy)acetic acid 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以38%的产率得到2-(4,5-Dibromo-2-(2-hydroxyacetyl)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-(2-hydroxyacetyl)thiophen-3-yl]oxyacetate 在 lithium hydroxide 、 硫酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 2-((4,5-dibromo-2-(2-(tert-butoxy)acetyl)thiophen-3-yl)oxy)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