1-<(2-aminoethoxy)methyl>thymine | 78137-59-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-<(2-aminoethoxy)methyl>thymine
• 英文别名: 5-methyl-1-(2'-aminoethoxymethyl)uracil；1-[(2-aminoethoxy)methyl]thymine；1-(2-Aminoethoxymethyl)-5-methylpyrimidine-2,4-dione
• CAS: 78137-59-4
• 化学式: C₈H₁₃N₃O₃
• 分子量: 199.21
• InChiKey: DQJXHAXYMJOASW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<(2-aminoethoxy)methyl>thymine 、 硫代异氰酸苯酯 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以86%的产率得到1-[2-[(5-Methyl-2,4-dioxo-pyrimidin-1-yl)methoxy]ethyl]-3-phenyl-thiourea
  参考文献：
  名称：

  Rational Design of 5‘-Thiourea-Substituted α-Thymidine Analogues as Thymidine Monophosphate Kinase Inhibitors Capable of Inhibiting Mycobacterial Growth

  摘要：

  Recently, thymidine monophosphate kinase (TMPK) emerged as an attractive target for developing inhibitors of Mycobacterium tuberculosis growth. The elucidation of the X-ray structure of TMPK of M. tuberculosis (TMPKmt), as well as the structure of an earlier serendipitously discovered dimeric thymidine inhibitor, laid the foundation for the design of potent and selective TMPKmt inhibitors reported here. Several hits identified within a series of 3'-C-branched thiourea-substituted P-thymidine derivatives inspired us to construct a set of 5'-thiourea-substituted a-thymidine derivatives characterized by a similar relative orientation of the thymine and arylthiourea moieties. (x-Thymidine derivative 15, featuring a (3-trifluoromethyl-4-chlorophenyl)thiourea moiety, has a K-i of 0.6 mu M and a selectivity index of 600 versus human TMPK. Moreover, it represents the first TMPK inhibitor showing good inhibitory activity on growing M. bovis (MIC99 = 20 mu g/mL) and M. tuberculosis (MIC50 = 6.25 mu g/mL) strains.

  DOI：

  10.1021/jm0706158
• 作为产物：
  描述：

  2,4-二甲氧基-5-甲基嘧啶 在 palladium on activated charcoal 吡啶 、 sodium hydroxide 、 叠氮化锂 、 氢气 、 sodium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 4.0~80.0 ℃ 、344.73 kPa 条件下， 反应 57.0h， 生成 1-<(2-aminoethoxy)methyl>thymine
  参考文献：
  名称：

  嘧啶无环核苷的合成

  摘要：

  尿苷，5-溴-，5-碘-和5-氟尿苷，胸苷和胞苷的核苷类似物是通过将适当取代的2,4-二甲氧基嘧啶与无环侧链缩合成苯甲酰化卤代醚的形式制备的，随后除去碱中的保护性苯甲酰基。2'- ø - p这些核苷类似物-tosylates然后可以修改成2'-卤代- ，叠氮基，和氨基衍生物。这些化合物中的许多是体外尿苷磷酸化酶的竞争性抑制剂，最活跃的是5-甲基-1-（2'-羟基乙氧基甲基）尿嘧啶。

  DOI：

  10.1002/jhet.5570180520

文献信息

• Synthesis and biological effects of acyclic pyrimidine nucleoside analogs
  作者：Alan C. Schroeder、Robert G. Hughes、Alexander Bloch

  DOI：10.1021/jm00141a012

  日期：1981.9

  K-12, the most potent among these, 1-[(2-hydroxyethoxy)methyl]-5-fluorouracil being active at an IC50 of 1.2 micro M. This compound was equally active in preventing the growth of a 5-fluorouracil resistant strain of E. coli. Some of the analogues were also found to selectively interfere with herpes simplex virus replication in vitro. None of the cytosine derivatives tested served as either substrates

  已经制备了一系列核苷类似物，其中环状碳水化合物部分被连接至胞嘧啶，胸腺嘧啶，尿嘧啶和5-氟尿嘧啶的脂族侧链取代。这些杂环的1-[（（2-羟基乙氧基）甲基]衍生物是通过使甲硅烷基化的碱与2-（氯甲氧基）乙基苯甲酸酯反应，然后用甲醇氨去除保护基而合成的。随后，许多这些衍生物的羟基被叠氮基，氨基或氨基甲酰氧基部分取代。还制备了胞嘧啶的1-（2-氧代-3-丁基）和1-（2-氧代-3-壬基）衍生物，它们的合成是通过使甲硅烷基化的杂环与适当的α-卤代酮缩合来完成的。在10（-4）M浓度下，新制备的化合物对培养中的白血病L-1210细胞无活性。但是，许多药物抑制了大肠杆菌K-12的体外生长，其中最有效的是1-[（（2-羟基乙氧基）甲基] -5-氟尿嘧啶，其IC50为1.2 microM。该化合物在阻止大肠杆菌的5-氟尿嘧啶抗性菌株的生长方面同样具有活性。还发现一些类似物在体外选择性干扰单纯疱疹病毒复制。
• Pyrimidine acyclic nucleosides. 5-Substituted 1-[(2-aminoethoxy)methyl]uracils as candidate antivirals
  作者：James L. Kelley、Mark P. Krochmal、Howard J. Schaeffer

  DOI：10.1021/jm00136a020

  日期：1981.4

  analogues of the acyclic aminonucleoside 1-[2-aminoethoxy)methyl]uracil (5) were prepared for evaluation as antivirals. The uracil and thymine analogues were prepared in two steps from N-[2-(chloromethoxy)ethyl]phthalimide (1). The 5-chloro, 5-bromo, and 5-iodo analogues were prepared by halogenation of 5. These acyclic aminonucleosides exhibited neither cell toxicity nor antiviral activity. This is

  制备了无环氨基核苷1- [2-氨基乙氧基）甲基]尿嘧啶（5）的几种5-取代类似物作为抗病毒剂进行评估。从N- [2-（氯甲氧基）乙基]邻苯二甲酰亚胺（1）分两步制备尿嘧啶和胸腺嘧啶类似物。通过卤化5制备5-氯，5-溴和5-碘类似物。这些无环氨基核苷既不显示细胞毒性也不显示抗病毒活性。这与它们缺乏对单纯疱疹病毒胸苷激酶的底物特性兼容。
• Synthesis of pyrimidine acyclonucleosides
  作者：H. M. Abrams、L. Ho、S. H. Chu

  DOI：10.1002/jhet.5570180520

  日期：1981.8

  Nucleoside analogues of uridine, 5-bromo-, 5-iodo-, and 5-fluorouridines, thymidine and cytidine were prepared by condensing appropriately substituted 2,4-dimethoxypyrimidines with an acyclic side chain in the form of a benzoylated halo-ether, and subsequent removal of the protecting benzoyl group in base. The 2′-O-p-tosylates of these nucleoside analogues could then be modified to 2′-halo-, azido-

  尿苷，5-溴-，5-碘-和5-氟尿苷，胸苷和胞苷的核苷类似物是通过将适当取代的2,4-二甲氧基嘧啶与无环侧链缩合成苯甲酰化卤代醚的形式制备的，随后除去碱中的保护性苯甲酰基。2'- ø - p这些核苷类似物-tosylates然后可以修改成2'-卤代- ，叠氮基，和氨基衍生物。这些化合物中的许多是体外尿苷磷酸化酶的竞争性抑制剂，最活跃的是5-甲基-1-（2'-羟基乙氧基甲基）尿嘧啶。
• Rational Design of 5‘-Thiourea-Substituted α-Thymidine Analogues as Thymidine Monophosphate Kinase Inhibitors Capable of Inhibiting Mycobacterial Growth
  作者：Ineke Van Daele、Hélène Munier-Lehmann、Matheus Froeyen、Jan Balzarini、Serge Van Calenbergh

  DOI：10.1021/jm0706158

  日期：2007.11.1

  Recently, thymidine monophosphate kinase (TMPK) emerged as an attractive target for developing inhibitors of Mycobacterium tuberculosis growth. The elucidation of the X-ray structure of TMPK of M. tuberculosis (TMPKmt), as well as the structure of an earlier serendipitously discovered dimeric thymidine inhibitor, laid the foundation for the design of potent and selective TMPKmt inhibitors reported here. Several hits identified within a series of 3'-C-branched thiourea-substituted P-thymidine derivatives inspired us to construct a set of 5'-thiourea-substituted a-thymidine derivatives characterized by a similar relative orientation of the thymine and arylthiourea moieties. (x-Thymidine derivative 15, featuring a (3-trifluoromethyl-4-chlorophenyl)thiourea moiety, has a K-i of 0.6 mu M and a selectivity index of 600 versus human TMPK. Moreover, it represents the first TMPK inhibitor showing good inhibitory activity on growing M. bovis (MIC99 = 20 mu g/mL) and M. tuberculosis (MIC50 = 6.25 mu g/mL) strains.