5-((((9H-fluoren-9-yl)methoxy)carbonylamino)methyl)thiophene-2-carboxylic acid | 476362-75-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 5-((((9H-fluoren-9-yl)methoxy)carbonylamino)methyl)thiophene-2-carboxylic acid
• 英文别名: 5-[(9H-fluoren-9-yl-methoxycarbonylamino)methyl]thiophene-2-carboxylic acid；5-(N-(9-fluorenylmethoxycarbonyl)aminomethyl)thiophen-2-carboxylic acid；5-(N-(Fmoc)aminomethyl)thiophen-2-carboxylic acid；5-[({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)methyl]thiophene-2-carboxylic acid；5-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]thiophene-2-carboxylic acid
• CAS: 476362-75-1
• 化学式: C₂₁H₁₇NO₄S
• 分子量: 379.436
• InChiKey: FTPSFRLVPGNHGC-UHFFFAOYSA-N

物化性质

• 沸点：
  635.6±55.0 °C(Predicted)
• 密度：
  1.367±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-((((9H-fluoren-9-yl)methoxy)carbonylamino)methyl)thiophene-2-carboxylic acid 在 三氟乙酸 作用下， 以 氯仿 、 水 为溶剂， 反应 1.0h， 生成 Inhibitor 47c
  参考文献：
  名称：

  Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design

  摘要：

  The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S-4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K-i = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K-i values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K-i = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.

  DOI：

  10.1021/jm020230j
• 作为产物：
  描述：

  5-溴-2-羧基噻吩 在 4-二甲氨基吡啶 、 正丁基锂 、 水 、 羟胺 、 碳酸氢钠 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 、 锌 作用下， 以 1,4-二氧六环 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 13.5h， 生成 5-((((9H-fluoren-9-yl)methoxy)carbonylamino)methyl)thiophene-2-carboxylic acid
  参考文献：
  名称：

  Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design

  摘要：

  The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S-4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K-i = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K-i values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K-i = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.

  DOI：

  10.1021/jm020230j

文献信息

• A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors
  作者：Claus G. Bang、Jakob F. Jensen、Emil O’Hanlon Cohrt、Lasse B. Olsen、Saba G. Siyum、Kim T. Mortensen、Tine Skovgaard、Jens Berthelsen、Liang Yang、Michael Givskov、Katrine Qvortrup、Thomas E. Nielsen

  DOI：10.1021/acscombsci.7b00068

  日期：2017.10.9

  readily available and nonintegral hydroxylamine linkers for the routine solid-phase synthesis of hydroxamic acids. The developed protocols enable the efficient synthesis and release of a wide range of hydroxamic acids from various resins, relying on high control and flexibility with respect to reagents and synthetic processes. A trityl-based hydroxylamine linker was used to synthesize a library of peptide

  我们在此提出了广泛有用的，容易获得的和非整体的羟胺连接基，用于羟肟酸的常规固相合成。所开发的方案能够有效地从各种树脂合成和释放各种异羟肟酸，这取决于试剂和合成方法的高度控制和灵活性。基于三苯甲基的羟胺接头用于合成肽异羟肟酸的文库。使用基于化学发光的测定法检查了化合物对7种HDAC酶亚型的抑制作用。