6-((E)-4-(((1-(5'-deoxy-2',3'-O,O-isopropylidene-adenosin-5'-yl)-1H-1,2,3-triazol-4-yl)methyl)amino)-3-methylbut-2-en-1-yl)-5-methoxy-4-methyl-7-((2-(trimethylsilyl)ethoxy)methoxy)isobenzofuran-1(3H)-one | 1229030-11-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-((E)-4-(((1-(5'-deoxy-2',3'-O,O-isopropylidene-adenosin-5'-yl)-1H-1,2,3-triazol-4-yl)methyl)amino)-3-methylbut-2-en-1-yl)-5-methoxy-4-methyl-7-((2-(trimethylsilyl)ethoxy)methoxy)isobenzofuran-1(3H)-one
• 英文别名: 6-[(E)-4-[[1-[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl]triazol-4-yl]methylamino]-3-methylbut-2-enyl]-5-methoxy-4-methyl-7-(2-trimethylsilylethoxymethoxy)-3H-2-benzofuran-1-one
• CAS: 1229030-11-8
• 化学式: C₃₇H₅₁N₉O₈Si
• 分子量: 777.953
• InChiKey: ATQSAEGEFOTCPQ-QDOKSDEJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.07
• 重原子数：
  55
• 可旋转键数：
  16
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  194
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  6-((E)-4-(((1-(5'-deoxy-2',3'-O,O-isopropylidene-adenosin-5'-yl)-1H-1,2,3-triazol-4-yl)methyl)amino)-3-methylbut-2-en-1-yl)-5-methoxy-4-methyl-7-((2-(trimethylsilyl)ethoxy)methoxy)isobenzofuran-1(3H)-one 在 水 、 三氟乙酸 作用下， 以80%的产率得到6-((E)-4-(((1-(5'-deoxy-adenosin-5'-yl)-1H-1,2,3-triazol-4-yl)-methyl)amino)-3-methylbut-2-en-1-yl)-7-hydroxy-5-methoxy-4-methylisobenzofuran-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：

  (E)-5-methoxy-4-methyl-6-(3-methyl-4-(prop-2-yn-1-ylamino)-but-2-en-1-yl)-7-((2-(trimethylsilyl)ethoxy)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64%的产率得到6-((E)-4-(((1-(5'-deoxy-2',3'-O,O-isopropylidene-adenosin-5'-yl)-1H-1,2,3-triazol-4-yl)methyl)amino)-3-methylbut-2-en-1-yl)-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

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.