1-(ethoxymethyl)-6-(phenylthio)thymine | 132774-39-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 1-(ethoxymethyl)-6-(phenylthio)thymine
• 英文别名: 1-ethoxymethyl-6-(phenylthio)thymine；1-(ethoxymethyl)-5-methyl-6-phenylsulfanylpyrimidine-2,4-dione
• CAS: 132774-39-1
• 化学式: C₁₄H₁₆N₂O₃S
• 分子量: 292.359
• InChiKey: KXTOSKMEVPRHSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(ethoxymethyl)-6-(phenylthio)thymine 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以71%的产率得到1-ethoxymethyl-3,4-dihydro-5-methyl-6-(phenylthio)-4-thioxopyrimidin-2(1H)-one
  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
• 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 11.0h， 生成 1-(ethoxymethyl)-6-(phenylthio)thymine
  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

• Synthesis and antiviral activity of deoxy analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents
  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/jm00103a009

  日期：1992.12

  substitution in the acyclic structure of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine (HEPT) on anti-HIV-1 activity was investigated by synthesizing a series of deoxy analogs and related compounds. Preparation of 1-[(2-alkyloxyethoxy)methyl]-6- (phenylthio)thymine (2-4) derivatives was carried out based on alkylation of HEPT with primary alkyl halides. Preparation of the 1-[(alkyloxy)methyl]-6-(phenylthio)thymine

  通过合成一系列脱氧类似物和相关化合物，研究了1-[（（2-羟基乙氧基）甲基] -6-（苯硫基）-胸腺嘧啶（HEPT）的无环结构中的取代对抗HIV-1活性的影响。基于HEPT与伯烷基卤化物的烷基化，进行1-[（（2-烷氧基乙氧基）甲基] -6-（苯硫基）胸腺嘧啶（2-4）衍生物的制备。进行了1-[（（烷氧基）甲基] -6-（苯硫基）胸腺嘧啶（26-31）和1-[（（烷氧基）甲基] -6-（芳硫基）-2-硫尿嘧啶（32-45）衍生物的制备根据LDA对1-[（（烷氧基）-甲基]胸腺嘧啶（9-14）和1-[（（烷氧基）甲基] -2-硫氧嘧啶（15-25）进行锂化反应，然后与二芳基二硫化物反应。2-硫尿嘧啶衍生物的氧化水解得到1-[（（烷氧基）甲基] -6-（芳硫基）尿嘧啶衍生物（46-57）。1-烷基-6-（苯硫基）胸腺嘧啶（59-61）衍生物是基于6-（苯硫基）胸腺嘧啶（58）的烷基化制备的。H
• TANAKA, HIROMICHI;BABA, MASANORI;SAITO, SHIGERU;MIYASAKA, TADASHI;TAKASHI+, J. MED. CHEM., 34,(1991) N, C. 1508-1511
  作者：TANAKA, HIROMICHI、BABA, MASANORI、SAITO, SHIGERU、MIYASAKA, TADASHI、TAKASHI+

  DOI：——

  日期：——
• Specific anti-HIV-1 acyclonucleosides which cannot be phosphorylated: synthesis of some deoxy analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine
  作者：Hiromichi Tanaka、Masanori Baba、Shigeru Saito、Tadashi Miyasaka、Hideaki Takashima、Kouichi Sekiya、Masaru Ubasawa、Issei Nitta、Richard T. Walker

  DOI：10.1021/jm00108a041

  日期：1991.4
• Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors
  作者：Raimon Puig-de-la-Bellacasa、Laura Giménez、Sofia Pettersson、Rosalia Pascual、Encarna Gonzalo、José A. Esté、Bonaventura Clotet、José I. Borrell、Jordi Teixidó

  DOI：10.1016/j.ejmech.2012.04.038

  日期：2012.8

  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, 21,2,3,1} 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.