tetraethyl (((6-(naphthalen-2-yl)thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis(phosphonate) | 1429012-45-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: tetraethyl (((6-(naphthalen-2-yl)thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis(phosphonate)
• CAS: 1429012-45-2
• 化学式: C₂₅H₃₁N₃O₆P₂S
• 分子量: 563.551
• InChiKey: IOSPBWKLIDAUHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.74
• 重原子数：
  37.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  108.87
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  tetraethyl (((6-(naphthalen-2-yl)thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis(phosphonate) 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 以29.5 mg的产率得到(((6-(naphthalen-2-yl)thieno[2,3-d]pyrimidin-4-yl)amino)methylene)diphosphonic acid
  参考文献：
  名称：

  发现人类法呢基焦磷酸合酶基于硫代嘧啶的抑制剂-通过三甲基甲硅烷基亚烷基中间体并行合成类似物

  摘要：

  基于硫代嘧啶的双膦酸酯被鉴定为人法呢基焦磷酸合酶（hFPPS）的一类新型的含氮双膦酸酯（N-BP）抑制剂。在元素硫的存在下，通过将2-（1-（三甲基甲硅烷基）亚乙基）丙二腈环化成2-氨基-4-（三甲基甲硅烷基）噻吩-3-甲腈来制备类似物。引导本位该中间导致了选择性碘化中C的-iododesilylation β在高效率的硫原子的。所开发的合成方案被用于结构平行的hFPPS的基于硫杂[2,3 - d ]嘧啶-4-胺的双膦酸酯抑制剂的合成。

  DOI：

  10.1016/j.bmc.2013.02.006
• 作为产物：
  描述：

  6-溴苯并[2,3-d]嘧啶-4-胺 在 potassium fluoride 、 四(三苯基膦)钯 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 0.33h， 生成 tetraethyl (((6-(naphthalen-2-yl)thieno[2,3-d]pyrimidin-4-yl)amino)methylene)bis(phosphonate)
  参考文献：
  名称：

  Thienopyrimidine Bisphosphonate (ThPBP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase: Optimization and Characterization of the Mode of Inhibition

  摘要：

  Human farnesyl pyrophosphate synthase (hFPPS) controls the post-translational prenylation of small GTPase proteins that are essential for cell signaling, cell proliferation, and osteoclast-mediated bone resorption. Inhibition of hFPPS is a clinically validated mechanism for the treatment of lytic bone diseases, including osteoporosis and cancer related bone metastases. A new series of thienopyrimidine-based bisphosphonates (ThP-BPs) were identified that inhibit hFPPS with low nanomolar potency. Crystallographic evidence revealed binding of ThP-BP inhibitors in the allylic subpocket of hFPPS. Simultaneous binding of inorganic pyrophosphate in the IPP subpocket leads to conformational closing of the active site cavity. The ThP-BP analogues are significantly less hydrophilic yet exhibit higher affinity for the bone mineral hydroxyapatite than the current N-BP drug risedronic acid. The antiproliferation properties of a potent ThB-BP analogue was assessed in a multiple myeloma cell line and found to be equipotent to the best current N-BP drugs. Consequently, these compounds represent a new structural class of hFPPS inhibitors and a novel scaffold for the development of human therapeutics.

  DOI：

  10.1021/jm400946f