5-isopropyl-6-(1-naphthylmethyl)-2-thiouracil | 640724-27-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-isopropyl-6-(1-naphthylmethyl)-2-thiouracil
• 英文别名: 6-(naphthalen-1-ylmethyl)-5-propan-2-yl-2-sulfanylidene-1H-pyrimidin-4-one
• CAS: 640724-27-2
• 化学式: C₁₈H₁₈N₂OS
• 分子量: 310.42
• InChiKey: RJQPTLMMYLVISP-UHFFFAOYSA-N

物化性质

• 熔点：
  228-232 °C(Solv: ethanol (64-17-5); ethyl acetate (141-78-6))
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-isopropyl-6-(1-naphthylmethyl)-2-thiouracil 在 氯乙酸 作用下， 以97%的产率得到5-isopropyl-6-(1-naphthylmethyl)uracil
  参考文献：
  名称：

  Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors: Part I. Synthesis and Structure-Activity Relationship of 1-Alkoxymethyl-5-alkyl-6-naphthylmethyl Uracils as HEPT Analogues

  摘要：

  合成了新型 1-[(2-羟乙氧基)甲基]-6-(苯硫基)胸腺嘧啶（HEPT）类似物--1-烷氧基甲基-5-烷基-6-萘甲基尿嘧啶，并将其评估为选择性和强效的非核苷类人类免疫缺陷病毒（HIV）-1 逆转录酶抑制剂。这些化合物的抗 HIV-1 活性是通过体外 HIV-1 感染 MT-4 和 CEM 生物测定法进行的。记录并计算了 EC50、CC50 和 SI。在 MT-4 和 CEM 细胞实验中，适当的位置，尤其是萘环的 1 位，可使药效显著提高。该系列中最重要的化合物是 1-乙氧基甲基-5-异丙基-6-（1-萘甲基）胸腺嘧啶 8l（IC50=17 nM，CC50=38332 nM、SI=2229）和 1-苄氧基甲基-5-乙基-6-(1-萘甲基)胸腺嘧啶 8n（IC50=17 nM，CC50=32560 nM，SI=1889）明显比 HEPT（EC50=7.0 μM，CD50=740 μM）明显更有效。

  DOI：

  10.1248/cpb.51.779
• 作为产物：
  描述：

  1-萘乙腈 在 sodium ethanolate 、 锌 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 6.0h， 生成 5-isopropyl-6-(1-naphthylmethyl)-2-thiouracil
  参考文献：
  名称：

  5-Alkyl-2-[(aryl and alkyloxylcarbonylmethyl)thio]-6-(1-naphthylmethyl) pyrimidin-4(3H)-ones as an unique HIV reverse transcriptase inhibitors of S-DABO series

  摘要：

  The introduction of a beta-carbonyl group to the C-2 side chain of S-DABO led to the finding of a series of novel potent anti-HIV agent. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations. Furthermore, the novel S-DABOs differ from the classical NNRTIs in that some compounds are active against both HIV-1 and HIV-2. They might interfere with another target or at least act on RT in a different way as compared to typical NNRTIs. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.04.008

文献信息

• Nonnucleoside HIV-1 reverse transcriptase inhibitors; part 3. Synthesis and antiviral activity of 5-alkyl-2-[(aryl and alkyloxyl-carbonylmethyl)thio]-6-(1-naphthylmethyl) pyrimidin-4(3H)-ones
  作者：Yanping He、Fener Chen、Xiongjie Yu、Yueping Wang、Erik De Clercq、Jan Balzarini、Christophe Pannecouque

  DOI：10.1016/j.bioorg.2004.05.007

  日期：2004.12

  beta-carbonyl group on the C-2 side chain were synthesized. All of the new compounds were evaluated for their anti-HIV activities in MT-4 cells. The most active compound, 5-isopropyl-2-[(4'-methoxyphenylcarbonyl-methyl)thio]-6-(1-naphthylmethyl)pyrimid in-4(3H)-one showed activity against HIV-1 and against the double mutated strain of HIV(Y181C and K103N) in the micromolar range. Furthermore, some

  合成了一系列在C-2侧链上具有β-羰基的6-萘甲基甲基取代的S-烷基化的二氢烷氧基苄基氧嘧啶（S-DABO）类似物。对所有这些新化合物在MT-4细胞中的抗HIV活性进行了评估。最活泼的化合物4-（3H）-中的5-异丙基-2-[（（4'-甲氧基苯基羰基-甲基）硫基] -6-（1-萘基甲基）嘧啶显示出对HIV-1和双突变的活性。 HIV的菌株（Y181C和K103N）在微摩尔范围内。此外，某些化合物在细胞培养中对HIV-1和HIV-2均具有活性。鉴于这些化合物针对S0561945进行测试时其抗病毒活性的损失远不如典型NNRTI的活性下降那么明显，
• Synthesis and anti-HIV-1 activity of S-dihydro(alkyloxy)benzyloxypyrimidine derivatives
  作者：Zhi-Kun Rao、Jing Long、Cong Li、Sui-Shuan Zhang、Mei He、Ling-Cheng Ou、Yong-Tang Zheng、Yan-Ping He

  DOI：10.1007/s00706-007-0834-8

  日期：2008.8

  Several 2-heteroaryl-, 2-heteroarylcarbonylmethyl-, 2-arylcarbonylmethyl, and 2-arylethyl derivatives of S-dihydro(alkyloxy)benzyloxypyrimidines have been synthesized and the anti-HIV activities of these compounds were tested in C8166 cell and against RT enzyme. It was found that some of these compounds showed good activity against HIV-1 (EC50 = 0.014-0.8 mu M) with low toxicity (CC50 value of 222-564 mu M) and high selectivity (SI value of 278-37743). The structure-activity relationships (SAR) of these compounds have also been discussed.
• Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors
  作者：Yue-Ping Wang、Fen-Er Chen、Erik De Clercq、Jan Balzarini、Christophe Pannecouque

  DOI：10.1016/j.ejmech.2008.06.028

  日期：2009.3

  A series of new 5-alkyl-2-benzylsulfanylpyrimidin-4(3H)-ones (5a-y) bearing different substituted arylmethyl moieties at the C-6 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against HIV-1 and HIV-2 in MT-4 cell cultures. The majority of the title compounds showed moderate to good activities against HIV-1 with an IC50 range from 6.67 mu M to 0.12 mu M. Among them, 6-(3,5-dimethylbenzy]) analogue 5q exhibited the most potent anti-HIV-1 activity (IC50 = 0.12 mu M, SI > 2642), which was about 40-fold more active than the reference compounds 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 2',3'-dideoxyinosine (DDI). The structure-activity relationships (SARs) of these new congeners were further discussed. (C) 2008 Elsevier Masson SAS. All rights reserved.