2-(hexylthio)pyrimidine-4,6-diamine | 1247673-99-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(hexylthio)pyrimidine-4,6-diamine
• 英文别名: 2-Hexylsulfanylpyrimidine-4,6-diamine
• CAS: 1247673-99-9
• 化学式: C₁₀H₁₈N₄S
• 分子量: 226.346
• InChiKey: CXOJZPHLYSSEKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(hexylthio)pyrimidine-4,6-diamine 在 盐酸 、 platinum(IV) oxide 、 H₄N⁽¹⁺⁾*O₄S^(2-) 、 氢气 、 溶剂黄146 、 六甲基二硅氮烷 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 为溶剂， 140.0 ℃ 、101.33 kPa 条件下， 反应 24.5h， 生成 2-hexylthio-8-azaadenosine
  参考文献：
  名称：

  Investigations into the Origin of the Molecular Recognition of Several Adenosine Deaminase Inhibitors

  摘要：

  Inhibitors of adenosine deaminase (ADA, EC 3 5 4 4) are potential therapeutic agents for the treatment of various health disorders Several highly potent inhibitors were previously identified, yet they exhibit unacceptable toxicities We performed a SAR study involving a series of C2 or C8 substituted purine-riboside analogues with a view to discover less potent inhibitors with a lesser toxicity We found that any substitution at C8 position of nebularine resulted in total loss of activity toward calf intestinal ADA However several 2-substituted-adenosine, 8-aza-adenosine, and nebularine analogues exhibited inhibitory activity Specifically, 2-Cl-purine riboside, 8-aza-2-thiohexyl adenosine, 2-thiohexyl adenosine, and 2-MeS-purine riboside were found to be competitive inhibitors of ADA with K-i values of 25, 22, 6, and 3 mu M, respectively We concluded that electronic parameters are not major recognition determinants of ADA but rather steric parameters A C2 substituent which fits ADA hydrophobic pocket and improves H-bonding with the enzyme makes a good inhibitor In addition, a gg rotamer about C4'-C5' bond is apparently an important recognition determinant

  DOI：

  10.1021/jm101286g
• 作为产物：
  描述：

  4,6-二氨基-2-巰基嘧啶 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以68%的产率得到2-(hexylthio)pyrimidine-4,6-diamine
  参考文献：
  名称：

  Synthesis, Dihydrofolate Reductase Inhibition, Anti-proliferative Testing, and Saturation Transfer Difference 1H-NMR Study of Some New 2-Substituted-4,6-diaminopyrimidine Derivatives

  摘要：

  合成了一系列2-取代-4,6-二氨基嘧啶衍生物并评估了它们的二氢叶酸还原酶（DHFR）抑制活性。饱和转移差(STD)1H-NMR实验用于探测化合物与人DHFR酶的结合特性。在酶测定研究中最有效的分子 12 和 15 在 STD 实验中显示出最好的结果，表明它们与受体的密切相互作用。随后进行对接研究，以解释观察到的配体和 DHFR 之间相互作用的结构基础。还在体外测定了所有化合物对 MCF-7、HepG2、SKHep1 和 Hela 肿瘤细胞系的生长抑制活性。化合物 16、17 和 22 在其他化合物中表现出最有效的体外抗增殖活性。

  DOI：

  10.1248/cpb.60.70

文献信息

• Investigations into the Origin of the Molecular Recognition of Several Adenosine Deaminase Inhibitors
  作者：Irina Gillerman、Bilha Fischer

  DOI：10.1021/jm101286g

  日期：2011.1.13

  Inhibitors of adenosine deaminase (ADA, EC 3 5 4 4) are potential therapeutic agents for the treatment of various health disorders Several highly potent inhibitors were previously identified, yet they exhibit unacceptable toxicities We performed a SAR study involving a series of C2 or C8 substituted purine-riboside analogues with a view to discover less potent inhibitors with a lesser toxicity We found that any substitution at C8 position of nebularine resulted in total loss of activity toward calf intestinal ADA However several 2-substituted-adenosine, 8-aza-adenosine, and nebularine analogues exhibited inhibitory activity Specifically, 2-Cl-purine riboside, 8-aza-2-thiohexyl adenosine, 2-thiohexyl adenosine, and 2-MeS-purine riboside were found to be competitive inhibitors of ADA with K-i values of 25, 22, 6, and 3 mu M, respectively We concluded that electronic parameters are not major recognition determinants of ADA but rather steric parameters A C2 substituent which fits ADA hydrophobic pocket and improves H-bonding with the enzyme makes a good inhibitor In addition, a gg rotamer about C4'-C5' bond is apparently an important recognition determinant
• Synthesis, Dihydrofolate Reductase Inhibition, Anti-proliferative Testing, and Saturation Transfer Difference 1H-NMR Study of Some New 2-Substituted-4,6-diaminopyrimidine Derivatives
  作者：Shohreh Mohebbi、Juan Manuel Falcón-Pérez、Esperanza González、Oscar Millet、Jose Maria Mato、Farzad Kobarfard

  DOI：10.1248/cpb.60.70

  日期：——

  A series of 2-substituted-4,6-diaminipyrimidine derivatives were synthesized and evaluated for their dihydrofolate reductase (DHFR) inhibitory activity. Saturation transfer difference (STD) 1H-NMR experiments were used to probe the binding characteristics of the compounds with human DHFR enzyme. The most potent molecules, 12 and 15, in enzyme assay study showed the best results in STD experiments indicating their intimate interaction with the receptor. The docking studies were followed to explain the structural basis for the observed interaction between the ligands and DHFR. All the compounds were also assayed in vitro for their growth inhibitory activity on MCF-7, HepG2, SKHep1, and Hela tumor cell lines. Compounds 16, 17, and 22 demonstrated the most potent in vitro anti-proliferative activity among the others.

  合成了一系列2-取代-4,6-二氨基嘧啶衍生物并评估了它们的二氢叶酸还原酶（DHFR）抑制活性。饱和转移差(STD)1H-NMR实验用于探测化合物与人DHFR酶的结合特性。在酶测定研究中最有效的分子 12 和 15 在 STD 实验中显示出最好的结果，表明它们与受体的密切相互作用。随后进行对接研究，以解释观察到的配体和 DHFR 之间相互作用的结构基础。还在体外测定了所有化合物对 MCF-7、HepG2、SKHep1 和 Hela 肿瘤细胞系的生长抑制活性。化合物 16、17 和 22 在其他化合物中表现出最有效的体外抗增殖活性。