5-methoxy-4-methyl-6-(2-(prop-2-yn-1-ylamino)ethyl)-7-((2-(trimethylsilyl)ethoxy1)methoxy)isobenzofuran-1(3H)-one | 1229030-07-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: 5-methoxy-4-methyl-6-(2-(prop-2-yn-1-ylamino)ethyl)-7-((2-(trimethylsilyl)ethoxy1)methoxy)isobenzofuran-1(3H)-one
• 英文别名: 5-methoxy-4-methyl-6-[2-(prop-2-ynylamino)ethyl]-7-(2-trimethylsilylethoxymethoxy)-3H-2-benzofuran-1-one
• CAS: 1229030-07-2
• 化学式: C₂₁H₃₁NO₅Si
• 分子量: 405.566
• InChiKey: KVDOSVUVVMPNFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.13
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-methoxy-4-methyl-6-(2-(prop-2-yn-1-ylamino)ethyl)-7-((2-(trimethylsilyl)ethoxy1)methoxy)isobenzofuran-1(3H)-one 、 5'-azido-5'-deoxy-2',3'-O-isopropylidene adenosine 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 3.0h， 以77%的产率得到6-(2-(((1-(5'-deoxy-2',3'-O,O-isopropylidene-adenosin-5'-yl)-1H-1,2,3-triazol-4-yl)methyl)amino)ethyl)-5-methoxy-4-methyl-7-((2-(trimethylsilyl)ethoxy)methoxy)isobenzofuran-1(3H)-one
  参考文献：
  名称：

  Triazole-Linked Inhibitors of Inosine Monophosphate Dehydrogenase from Human and Mycobacterium tuberculosis

  摘要：

  The modular nature of nicotinamide adenine dinucleotide (NAD)-mimicking inosine monophsophate dehydrogenase (IMPDH) inhibitors has prompted us to investigate novel mycophenolic adenine dinucleotides (MAD) in which 1,2,3-triazole linkers were incorporated as isosteric replacements of the pyrophosphate linker. Synthesis and evaluation of these inhibitors led to identification of low nanomolar inhibitors of human IMPDH and more importantly the first potent inhibitor of IMPDH from Mycobacterium tuberculosis (mtIMPDH). Computational studies of these IMPDH enzymes helped rationalize the observed structure-activity relationships. Additionally, the first cloning, expression, purification and characterization of mtIMPDH is reported.

  DOI：

  10.1021/jm100424m
• 作为产物：
  描述：

  2-(6-methoxy-7-methyl-3-oxo-4-((2-(trimethylsilyl)ethoxy)methoxy)-1,3-dihydroisobenzofuran-5-yl)acetaldehyde 、 炔丙胺 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 4.0h， 以86%的产率得到5-methoxy-4-methyl-6-(2-(prop-2-yn-1-ylamino)ethyl)-7-((2-(trimethylsilyl)ethoxy1)methoxy)isobenzofuran-1(3H)-one
  参考文献：
  名称：

  Triazole-Linked Inhibitors of Inosine Monophosphate Dehydrogenase from Human and Mycobacterium tuberculosis

  摘要：

  The modular nature of nicotinamide adenine dinucleotide (NAD)-mimicking inosine monophsophate dehydrogenase (IMPDH) inhibitors has prompted us to investigate novel mycophenolic adenine dinucleotides (MAD) in which 1,2,3-triazole linkers were incorporated as isosteric replacements of the pyrophosphate linker. Synthesis and evaluation of these inhibitors led to identification of low nanomolar inhibitors of human IMPDH and more importantly the first potent inhibitor of IMPDH from Mycobacterium tuberculosis (mtIMPDH). Computational studies of these IMPDH enzymes helped rationalize the observed structure-activity relationships. Additionally, the first cloning, expression, purification and characterization of mtIMPDH is reported.

  DOI：

  10.1021/jm100424m

文献信息

• Triazole-Linked Inhibitors of Inosine Monophosphate Dehydrogenase from Human and <i>Mycobacterium tuberculosis</i>
  作者：Liqiang Chen、Daniel J. Wilson、Yanli Xu、Courtney C. Aldrich、Krzysztof Felczak、Yuk Y. Sham、Krzysztof W. Pankiewicz

  DOI：10.1021/jm100424m

  日期：2010.6.24

  The modular nature of nicotinamide adenine dinucleotide (NAD)-mimicking inosine monophsophate dehydrogenase (IMPDH) inhibitors has prompted us to investigate novel mycophenolic adenine dinucleotides (MAD) in which 1,2,3-triazole linkers were incorporated as isosteric replacements of the pyrophosphate linker. Synthesis and evaluation of these inhibitors led to identification of low nanomolar inhibitors of human IMPDH and more importantly the first potent inhibitor of IMPDH from Mycobacterium tuberculosis (mtIMPDH). Computational studies of these IMPDH enzymes helped rationalize the observed structure-activity relationships. Additionally, the first cloning, expression, purification and characterization of mtIMPDH is reported.