iodomethyl 2-(2-(2-methoxyethoxy)ethoxy)ethyl carbonate | 431894-42-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机碳酸及其衍生物
• 英文名称: iodomethyl 2-(2-(2-methoxyethoxy)ethoxy)ethyl carbonate
• 英文别名: Iodomethyl 2-(2-(2-methoxyethoxy)-ethoxy)-ethyl carbonate；iodomethyl 2-[2-(2-methoxyethoxy)ethoxy]ethyl carbonate
• CAS: 431894-42-7
• 化学式: C₉H₁₇IO₆
• 分子量: 348.135
• InChiKey: HYBUVZNAILLNHN-UHFFFAOYSA-N

物化性质

• 沸点：
  339.8±32.0 °C(Predicted)
• 密度：
  1.548±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  iodomethyl 2-(2-(2-methoxyethoxy)ethoxy)ethyl carbonate 、 N-cyano-N'-(9-diethylphosphinoyloxynonyl)-N''-4-pyridylguanidine 在 盐酸 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 生成 1-[2-(2-(2-Methoxyethoxy)-ethoxy)-ethoxy-carbonyloxymethyl]-4-[N'-cyano-N"-(9-(diethoxyphosphinoyloxy)-nonyl)-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：

  三甘醇单甲醚 在 吡啶 、 sodium iodide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 iodomethyl 2-(2-(2-methoxyethoxy)ethoxy)ethyl carbonate
  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

• Soft Alkyl Ether Prodrugs of a Model Phenolic Drug: The Effect of Incorporation of Ethyleneoxy Groups on Transdermal Delivery
  作者：Joshua Thomas、Susruta Majumdar、Kenneth Sloan

  DOI：10.3390/molecules14104231

  日期：——

  Two different types of soft alkyl ether prodrugs incorporating ethyleneoxy groups into the promoiety have been synthesized for a model phenol (acetaminophen, APAP): alkyloxycarbonyloxymethyl type (AOCOM) and N-alkyl-N-alkyloxycarbonyl-aminomethyl type (NANAOCAM). The solubilities in isopropyl myristate, S(IPM), and water, S(AQ), partition coefficients between IPM and pH 4.0 buffer, K(IPM:4.0), and

  已经为模型苯酚（对乙酰氨基酚，APAP）合成了两种不同类型的软烷基醚前药，这些前药将亚乙基氧基基团并入前体部分：烷氧基羰基氧基甲基型（AOCOM）和 N-烷基-N-烷氧基羰基-氨基甲基型（NANAOCAM）。肉豆蔻酸异丙酯 S(IPM) 和水 S(AQ) 中的溶解度、IPM 和 pH 4.0 缓冲液之间的分配系数 K(IPM:4.0)，以及通过无毛小鼠皮肤从 IPM 递送含有 APAP 的总物种， J(MMIPM)，已经测量了前药。J(MMIPM) 值由 Roberts-Sloan (RS) 方程准确预测。每种类型仅实现了 JMMIPM 的适度增长（约 1.4 倍）。唯一比APAP更水溶性和更脂溶性的前药没有改善APAP的J(MMIPM)。
• [EN] PHENAZINE DERIVATIVES AS ANTIMICROBIAL AGENTS<br/>[FR] DÉRIVÉS DE PHÉNAZINE UTILISÉS COMME AGENTS ANTIMICROBIENS
  申请人：UNIV FLORIDA

  公开号：WO2018152436A8

  公开（公告）日：2019-09-12
• CYANOGUANIDINE PRODRUGS
  申请人：Leo Pharma A/S

  公开号：EP1339686A2

  公开（公告）日：2003-09-03
• US6525077B2
  申请人：——

  公开号：US6525077B2

  公开（公告）日：2003-02-25
• [EN] CYANOGUANIDINE PRODRUGS<br/>[FR] PROMEDICAMENTS A BASE DE CYANOGUANIDINE
  申请人：LEO PHAMRACEUTICAL PRODUCTS LT

  公开号：WO2002042265A2

  公开（公告）日：2002-05-30

  The invention relates to compounds of formula (I), wherein X1 and X2 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 hycrocarbon radical, hydroxyl, halogen, amino, nitro, cyano, aminosulfonyl, alkylsulfonylamino, alkylcarbonyl, formyl, aminocarbonyl or alkylcarbonylamino; Y1 and Y2 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, SO2-N(R'), methylene or N(R')-SO2 wherein R' et R'' independently represent straight or branched hydrocarbon diradicals containing up to 4 carbon atoms; Y3 represents O, O-C(O), C(O)-O, N(R8), R8 being hydrogen or C1-4alkyl; R1 represents hydrogen or straight, branched and/or cyclic alkyl, optionally substituted with phenyl; or an aromatic hydrocarbon radical; R2 represents aryl, heteroaryl or a non-aromatic heterocyclic hydrocarbon radical, all of which are optionally substituted; tetrahydropyranyloxy, di-(C1-4 alkoxy)phosphinoyloxy or C1-4 alkoxycarbonylamino; R3 represents hydrogen; a straight, branched and/or cyclic hydrocarbon radical, optionally substituted with one or more amino, hydroxy, carboxy, halogen, nitro, cyano, alcoxy, aminocarbonyl, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, 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, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, sulfo, hydroxysulfonyloxy, dihydroxyphosphinoyloxy, phosphono, sulfamino, aminosulfonyl, aminoacylamino or dialkoxyphosphinoyl; (a) wherein s is an integer from 1 to 200; R6 is hydrogen or an optionally substituted non-aromatic hydrocarbon radical; R7 Is independently hydrogen or methyl; R4 and R5 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.