6-(3-氯苯基)硫烷基-1-(2-羟基乙氧基甲基)-5-甲基嘧啶-2,4-二酮 | 125056-61-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: 6-(3-氯苯基)硫烷基-1-(2-羟基乙氧基甲基)-5-甲基嘧啶-2,4-二酮
• 英文名称: 6-<(3-chlorophenyl)thio>-1-<(2-hydroxyethoxy)methyl>thymine
• 英文别名: 1-[(2-hydroxyethoxy)methyl]-6-(3-chlorophenylthio)thymine；6-((3-Chlorophenyl)thio)-1-((2-hydroxyethoxy)methyl)thymine；6-(3-chlorophenyl)sulfanyl-1-(2-hydroxyethoxymethyl)-5-methylpyrimidine-2,4-dione
• CAS: 125056-61-3
• 化学式: C₁₄H₁₅ClN₂O₄S
• 分子量: 342.803
• InChiKey: XAZQEUGIDTXFHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-甲基嘧啶-2,4,6(1H,3H,5H)-三酮 在 sodium tetrahydroborate 、 N,O-双三甲硅基乙酰胺 、 苄基三乙基氯化铵 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 7.5h， 生成 6-(3-氯苯基)硫烷基-1-(2-羟基乙氧基甲基)-5-甲基嘧啶-2,4-二酮
  参考文献：
  名称：

  Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors

  摘要：

  New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 2{1,2,3,1} and 2 {1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC50 = 0.015 mu g/mL; 0.046 mu M, SI > 1667) and (EC50 = 0.025 mu g/mL; 0.086 mu M, SI > 1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC50 = 1.01 mu g/ml; 3.27 mu M, SI > 25). (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.04.038

文献信息

• Structure-activity relationships of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine analogs: effect of substitutions at the C-6 phenyl ring and at the C-5 position on anti-HIV-1 activity
  作者：Hiromichi Tanaka、Hideaki Takashima、Masaru Ubasawa、Kouichi Sekiya、Issei Nitta、Masanori Baba、Shiro Shigeta、Richard T. Walker、Erik De Clercq、Tadashi Miyasaka

  DOI：10.1021/jm00080a020

  日期：1992.1

  pyrimidine moiety of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-2-thiothymine (HEPT-S) on anti-HIV-1 activity was investigated by synthesizing a series of 5-methyl-6-(arylthio) and 5-substituted-6-(phenylthio) derivatives. Preparation of the 5-methyl-6-(arylthio) derivatives was carried out based on either LDA lithiation of 1-[[2-(tert-butyld

  取代对1-[（2-羟基乙氧基）甲基] -6-（苯硫基）胸腺嘧啶（HEPT）和1-[（（2-羟基乙氧基）甲基] -6-（苯硫基）-2-硫胸腺嘧啶的嘧啶部分的影响通过合成一系列的5-甲基-6-（芳硫基）和5-取代的6-（苯硫基）衍生物，研究了（HEPT-S）的抗HIV-1活性。根据1-[[2-（叔丁基二甲基甲硅烷氧基）乙氧基]甲基]胸腺嘧啶（3）和1-[[2-（叔丁基）的LDA锂化反应来制备5-甲基-6-（芳硫基）衍生物。 -丁基丁基二甲基甲硅烷氧基）乙氧基]甲基] -2-硫胸腺嘧啶（4），然后与二芳基二硫化物反应或1-[[[2-（叔丁基二甲基甲硅烷氧基）乙氧基]-甲基] -6-（苯基亚磺酰基）胸腺嘧啶的加成消除反应（31）与芳族硫醇。基于1-[[[2-（叔丁基二甲基甲硅烷氧基）乙氧基]甲基] -6-（苯硫基）尿嘧啶的C-5锂化反应制备5-取代的6-（苯硫基）衍生物（41 ）用LTMP或LDA
• 6-SUBSTITUTED ACYCLICPYRIMIDINE NUCLEOSIDE DERIVATIVES AND ANTIVIRAL AGENTS CONTAINING SAME AS ACTIVE INGREDIENTS
  申请人：Mitsubishi Chemical Corporation

  公开号：EP0371139B1

  公开（公告）日：1994-10-12
• US5112835A
  申请人：——

  公开号：US5112835A

  公开（公告）日：1992-05-12