1-[3-(N-tert-butoxycarbonylamino)-propyl-carbamoyloxymethyl]-4-[N'-cyano-N"-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium iodide | 432037-72-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-[3-(N-tert-butoxycarbonylamino)-propyl-carbamoyloxymethyl]-4-[N'-cyano-N"-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium iodide
• 英文别名: 1-[3-(N-tert-butoxycarbonylamino)-propyl-carbamoyloxymethyl]-4-[N'-cyano-N''-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium iodide；tert-butyl N-[3-[[4-[[N'-[6-(4-chlorophenoxy)hexyl]-N-cyanocarbamimidoyl]amino]pyridin-1-ium-1-yl]methoxycarbonylamino]propyl]carbamate;iodide
• CAS: 432037-72-4
• 化学式: C₂₉H₄₁ClN₇O₅*I
• 分子量: 730.046
• InChiKey: LIIHOUCEDGVYMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.71
• 重原子数：
  43
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  150
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-[3-(N-tert-butoxycarbonylamino)-propyl-carbamoyloxymethyl]-4-[N'-cyano-N"-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium iodide 生成 1-[3-Aminopropyl-carbamoyloxymethyl]-4-[N'-cyano-N''-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium chloride
  参考文献：
  名称：

  Cyanoguanidine prodrugs

  摘要：

  该发明涉及以下式I的化合物： 其中X1和X2分别表示键；一种直链、支链和/或环烃二自由基，可选择地取代一个或多个羟基、卤素、硝基、氨基、氰基、氨基磺酰基、烷基磺酰胺基、烷基羰基、甲酰基、氨基羰基或烷基羰基氨基；一种杂芳烃基或非芳香杂环烃二自由基，均可选择地取代一个或多个直链、支链和/或环非芳香烃基、羟基、卤素、氨基、硝基、氰基、氨基磺酰基、烷基磺酰胺基、烷基羰基、甲酰基、氨基羰基或烷基羰基氨基； Y1和Y2分别表示键、醚二自由基（R′—O—R″）、胺二自由基（R′—N—R″）、O、S、S(O)、S(O)2、C(O)、NH—CO、CO—NH、SO2—N(R′)、亚甲基或N(R′)—SO2，其中R′和R″分别表示含有最多4个碳原子的直链或支链烃基； Y3表示O、O—C(O)、C(O)—O、N(R8)，其中R8为氢或C1-4烷基 R1表示氢或直链、支链和/或环烷基，可选择地取代苯基；或芳香烃基； R2表示芳基、杂芳基或非芳香杂环烃基，均可选择地取代；四氢吡喃氧基、二-(C1-4烷氧)磷酰氧基或C1-4烷氧羰基氨基； R3表示氢；一种直链、支链和/或环烃基，可选择地取代一个或多个氨基、羟基、羧基、卤素、硝基、氰基、烷氧基、氨基羰基、C1-4烷氧羰基、C1-4烷氧羰基氨基、磺酰基、羟基磺酰氧基、二羟基磷酰氧基、磷酸酯、磺胺基、氨基磺酰基、氨基酰氨基或二烷氧基磷酰基；杂芳基或非芳香杂环烃基，均可选择地取代一个或多个直链、支链和/或环烃基、氨基、羟基、羧基、卤素、硝基、氰基、烷氧基、氨基羰基、C1-4烷氧羰基、C1-4烷氧羰基氨基、磺酰基、羟基磺酰氧基、二羟基磷酰氧基、磷酸酯、磺胺基、氨基磺酰基、氨基酰氨基或二烷氧基磷酰基； 其中s为1至200的整数；R6为氢或可选择地取代的非芳香烃基；R7独立地为氢或甲基； R4和R5独立地表示氢；一种直链、支链和/或环烃基，可选择地取代卤素、羟基、卤素、氨基、硝基或氰基； A表示氢、可选择地取代的直链、支链和/或环烃基、羟基、卤素、硝基、氰基、杂芳基、杂芳基烷基或硫醇；m和r独立地为0至4的整数；n为0或1； Z-为药用可接受的阴离子，如氯化物、溴化物、碘化物、硫酸盐、甲磺酸盐、对甲苯磺酸盐、硝酸盐或磷酸盐。这些化合物非常适用于人类和兽医治疗中作为前药。

  公开号：

  US20020165201A1
• 作为产物：
  描述：

  chloromethyl N-(3-(N-tert-butoxycarbonylamino)propyl) carbamate 在 sodium iodide 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 0.33h， 生成 1-[3-(N-tert-butoxycarbonylamino)-propyl-carbamoyloxymethyl]-4-[N'-cyano-N"-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium iodide
  参考文献：
  名称：

  EB1627: a soluble prodrug of the potent anticancer cyanoguanidine CHS828

  摘要：

  To overcome pharmacokinetic and solubility problems observed in early clinical trials with the potent anticancer compound CHS828, we synthesised a series of prodrugs with improved properties. The best compound obtained was EB1627, with a tetraethyleneglycol moiety attached to the parent drug via a carbonate linkage. This compound was found soluble enough to be given i.v. and the drug was rapidly released in vivo exerting a very potent inhibitory activity alone and in combination with known cytostatics (etoposide) in animal models in vivo. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.064

文献信息

• Compositions and Methods for Effecting NAD+ Levels Using A Nicotinamide Phosphoribosyl Tranferase Inhibitor
  申请人：Roulston Anne

  公开号：US20090162454A1

  公开（公告）日：2009-06-25

  The present invention relates to methods for decreasing cellular DNA repair in a target patient; decreasing cellular NAD + biosynthesis in a target patient; increasing efficiency of radiation therapy in a target patient; modulating nicotinamide phosphoribosyl transferase activity in a patient; or sensitizing a patient to a DNA damaging therapy. The invention relates to methods for treating a patient who received a toxic dose of an nicotinamide phosphoribosyl transferase inhibitor. The invention also relates to pharmaceutical compositions comprising a physiologically acceptable carrier; an effective amount of a NMPRT inhibitor; and nicotinic acid. The invention also relates to methods for treating a patient diagnosed with or suspected to have a cancer deficient in nicotinic acid pathway.
• COMPOSITIONS AND METHODS FOR EFFECTING NAD+ LEVELS USING A NICOTINAMIDE PHOSPHORIBOSYL TRANSFERASE INHIBITOR
  申请人：Roulston Anne

  公开号：US20090215823A1

  公开（公告）日：2009-08-27

  The present invention relates to methods for decreasing cellular DNA repair in a patient diagnosed with or suspected to have chronic lymphocytic leukemia (CLL); decreasing cellular NAD + biosynthesis in a patient diagnosed with or suspected to have CLL; or sensitizing a patient diagnosed with or suspected to have CLL to a DNA damaging therapy. The invention relates to methods for treating a patient diagnosed with or suspected to have CLL.
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  公开号：US6525077B2

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  公开（公告）日：2012-07-03