iodomethyl N-(3-(N-tert-butoxycarbonylamino)propyl) carbamate | 432037-40-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: iodomethyl N-(3-(N-tert-butoxycarbonylamino)propyl) carbamate
• 英文别名: Iodomethyl N-(3-(N-tert-butoxycarbonylamino)-propyl)-carbamate；tert-butyl N-[3-(iodomethoxycarbonylamino)propyl]carbamate
• CAS: 432037-40-6
• 化学式: C₁₀H₁₉IN₂O₄
• 分子量: 358.176
• InChiKey: TYPKILRVJPMEMV-UHFFFAOYSA-N

物化性质

• 沸点：
  425.3±30.0 °C(Predicted)
• 密度：
  1.510±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  iodomethyl N-(3-(N-tert-butoxycarbonylamino)propyl) carbamate 在 盐酸 作用下， 以 乙醚 、 乙腈 为溶剂， 反应 0.33h， 生成 1-[3-Aminopropyl-carbamoyloxymethyl]-4-[N'-cyano-N''-(6-(4-chlorophenoxy)-hexyl)-N-guanidino]-pyridinium chloride
  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
• 作为产物：
  描述：

  N-叔丁氧羰基-1,3-丙二胺 在 三乙胺 、 sodium iodide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 iodomethyl N-(3-(N-tert-butoxycarbonylamino)propyl) carbamate
  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

• Cyanoguanidine prodrugs
  申请人：——

  公开号：US20020165201A1

  公开（公告）日：2002-11-07

  The invention relates to compounds of the formula I 1 wherein X 1 and X 2 independently represent a bond; a straight, branched and/or cyclic hydrocarbon diradical, optionally substituted with one or more hydroxy, halogen, nitro, amino, cyano, aminosulfonyl, alkylsulfonylamino, alkylcarbonyl, formyl, aminocarbonyl or alkylcarbonylamino; a heteroarylene or non-aromatic heterocyclic hydrocarbon diradical, all of which are optionally substituted with one or more straight, branched and/or cyclic non-aromatic hydrocarbon radical, hydroxyl, halogen, amino, nitro, cyano, aminosulfonyl, alkylsulfonylamino, alkylcarbonyl, formyl, aminocarbonyl or alkylcarbonylamino; Y 1 and Y 2 independently represent a bond, an ether diradical (R′—O—R″), an amine diradical (R′—N—R″), O, S, S(O), S(O) 2 , C(O), NH—CO, CO—NH, SO 2 —N(R′), methylene or N(R′)—SO 2 wherein R′ and R″ independently represent straight or branched hydrocarbon diradicals containing up to 4 carbon atoms; Y 3 represents O, O—C(O), C(O)—O, N(R 8 ), R 8 being hydrogen or C 1-4 alkyl R 1 represents hydrogen or straight, branched and/or cyclic alkyl, optionally substituted with phenyl; or an aromatic hydrocarbon radical; R 2 represents aryl, heteroaryl or a non-aromatic heterocyclic hydrocarbon radical, all of which are optionally substituted; tetrahydropyranyloxy, di-(C 1-4 alkoxy)phosphinoyloxy or C 1-4 alkoxycarbonylamino; R 3 represents hydrogen; a straight, branched and/or cyclic hydrocarbon radical, optionally substituted with one or more amino, hydroxy, carboxy, halogen, nitro, cyano, alkoxy, aminocarbonyl, C 1-4 alkoxycarbonyl, C 1-4 alkoxycarbonylamino, sulfo, hydroxysulfonyloxy, dihydroxyphosphinoyloxy, phosphono, sulfamino, aminosulfonyl, aminoacylamino or dialkoxyphosphinoyl; heteroaryl or a non-aromatic heterocyclic hydrocarbon radical, all of which are optionally substituted with one or more straight, branched and/or cyclic hydrocarbon radical, amino, hydroxy, carboxy, halogen, nitro, cyano, alkoxy, aminocarbonyl, C 1-4 alkoxycarbonyl, C 1-4 alkoxycarbonylamino, sulfo, hydroxysulfonyloxy, dihydroxyphosphinoyloxy, phosphono, sulfamino, aminosulfonyl, aminoacylamino or dialkoxyphosphinoyl; 2 wherein s is an integer from 1 to 200; R 6 is hydrogen or an optionally substituted non-aromatic hydrocarbon radical; R 7 is independently hydrogen or methyl; R 4 and R 5 independently represent hydrogen; a straight, branched and/or cyclic hydrocarbon radical, optionally substituted with halogen, hydroxyl, halogen, amino, nitro or cyano; A represents hydrogen, an optionally substituted, straight, branched and/or cyclic hydrocarbon radical, hydroxy, halogen, nitro, cyano, heteroaryl, heteroaralkyl or thiol; m and r are independently integers from 0 to 4; and n is 0 or 1; Z − is a pharmaceutically acceptable anion, such as chloride, bromide, iodide, sulfate, methanesulfonate, p-toluenesulfonate, nitrate or phosphate. The compounds are well suited as prodrugs in human and veterinary therapy.

  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。