5-isopropyl-2-[(methylthiomethyl)thio]-6-(3,5-dimethylbenzyl)-pyrimidin-4-1H-one | 210645-96-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 5-isopropyl-2-[(methylthiomethyl)thio]-6-(3,5-dimethylbenzyl)-pyrimidin-4-1H-one
• 英文别名: 6-(3,5-Dimethyl-benzyl)-5-isopropyl-2-methylsulfanylmethylsulfanyl-3H-pyrimidin-4-one；4-[(3,5-dimethylphenyl)methyl]-2-(methylsulfanylmethylsulfanyl)-5-propan-2-yl-1H-pyrimidin-6-one
• CAS: 210645-96-8
• 化学式: C₁₈H₂₄N₂OS₂
• 分子量: 348.533
• InChiKey: LLRHMUNEFHEADF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  92.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-溴代异戊酸乙酯 在 sodium ethanolate 、 potassium carbonate 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 5-isopropyl-2-[(methylthiomethyl)thio]-6-(3,5-dimethylbenzyl)-pyrimidin-4-1H-one
  参考文献：
  名称：

  新型二氢烷氧基苄基氧嘧啶衍生物作为人免疫缺陷病毒逆转录酶的有效非核苷抑制剂的基于结构的设计。

  摘要：

  基于NNI结合袋的结构设计了两种针对人免疫缺陷病毒（HIV）逆转录酶（RT）的非核苷抑制剂（NNI）结合位点的高效二氢烷氧基苄基氧嘧啶（DABO）衍生物，并测试了其抗HIV活性。我们的主要DABO衍生物5-异丙基-2-[（（甲硫基甲基）硫代] -6-（苄基）-嘧啶-4-（1H）-on e产生了对纯化的重组HIV RT的有效抑制活性，并废除了外围的HIV复制纳摩尔浓度（50％抑制浓度，<1 nM）的血液单核细胞，但在高达100 microM的浓度下未显示可检测的细胞毒性。

  DOI：

  10.1128/aac.42.12.3225

文献信息

• 5-Alkyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-ones as potent non-nucleoside reverse transcriptase inhibitors of S-DABO series
  作者：Rakesh Vig、Chen Mao、T.K. Venkatachalam、Lisa Tuel-Ahlgren、Elise A. Sudbeck、Fatih M. Uckun

  DOI：10.1016/s0960-894x(98)00250-9

  日期：1998.6

  Novel dihydroalkoxybenzyloxopyrimidine (S-DABO) derivatives targeting the non-nucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been synthesized using a novel computer model for the NNI binding pocket and tested for their RT inhibitory activity in cell-free assays using purified recombinant HIV RT as well as for their anti-HIV activity in

  使用新型计算机模型将NNI结合袋合成了靶向人免疫缺陷病毒（HIV）逆转录酶（RT）的非核苷抑制剂（NNI）结合位点的新型二氢烷氧基苄基氧嘧啶（S-DABO）衍生物，并测试了其对RT的抑制作用使用纯化的重组HIV RT进行的无细胞检测中的抗HIV活性以及在HTL VIIIB感染的外周血单核细胞中的抗HIV活性。我们的计算方法允许鉴定几个配体衍生位点，以产生更有效的S-DABO衍生物。我们的铅S-DABO衍生物5-异丙基-2-[[（甲硫基甲基）硫代] -6-（苄基）-嘧啶-4-（1H）-一（化合物3），
• Gel-microemulsion formulations
  申请人：——

  公开号：US20030083314A1

  公开（公告）日：2003-05-01

  A pharmaceutical composition adapted for use as a spermicide, the composition comprising a gel-microemulsion comprising an oil-in-water microemulsion and a polymeric hydrogel. The gel-microemulsion can be used in a spermicidal method. Also, a gel-microemulsion pharmaceutical composition adapted for use as a formulation base for additional therapeutic agents. Examples of additional agents include, anti-microbial agents and spermicidal agents. Such gel-microemulsions with additional therapeutic agents can be used in methods for appropriate therapeutic treatment. Also, a gel-microemulsion pharmaceutical composition that is adapted for use as both a spermicide and formulation base for anti-microbial agents to provide a dual function contraceptive/anti-microbial formulation. Method of using such a composition as a dual function contraceptive/anti-microbial formulation are also included.

  一种适用于作为精子杀死剂的制药组合物，该组合物包括一种凝胶微乳液，其中包括一种油包水微乳液和一种聚合物水凝胶。该凝胶微乳液可用于精子杀死方法。此外，一种适用于作为附加治疗剂的配方基础的凝胶微乳液制药组合物。附加剂例子包括抗微生物剂和精子杀死剂。这种带有附加治疗剂的凝胶微乳液可以用于适当的治疗方法。此外，一种适用于作为既是精子杀死剂又是抗微生物剂配方基础的凝胶微乳液制药组合物，以提供双重功能避孕/抗微生物制剂。使用这种组合物作为双重功能避孕/抗微生物制剂的方法也包括在内。
• Nonnucleoside inhibitors of reverse transcriptase for the treatment of HIV infection
  申请人：Parker Hughes Institute

  公开号：EP1528057A1

  公开（公告）日：2005-05-04

  Novel compounds that are potent inhibitors of HIV reverse transcriptase (RT) are described in the invention. These novel compounds also inhibit replication of a retrovirus, such as human immunodeficiency virus-1 (HIV-I). The novel compounds of the invention include analogs and derivatives of phenethylthiazolylthiourea (PETT), of dihydroalkoxybenzy-loxopyrimidine (DABO), and of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). The invention additionally provides a composite HIV reverse-transcriptase (RT) nonnucleoside inhibitor (NNI) binding pocket constructed from a composite of multiple NNI-RT complexes. The composite RT-NNI binding pocket provides a unique and useful tool for designing and identifying novel, potent inhibitors of reverse transcriptase.

  本发明描述了对 HIV 逆转录酶（RT）具有强效抑制作用的新型化合物。这些新型化合物还能抑制逆转录病毒（如人类免疫缺陷病毒-1（HIV-I））的复制。本发明的新型化合物包括苯乙基噻唑基硫脲（PETT）、二氢烷氧基苄基环嘧啶（DABO）和 1-[(2-羟基乙氧基)甲基]-6-(苯硫基)胸腺嘧啶（HEPT）的类似物和衍生物。本发明还提供了一种复合 HIV 逆转录酶（RT）非核苷抑制剂（NNI）结合袋，该结合袋由多个 NNI-RT 复合物复合而成。复合 RT-NNI 结合袋为设计和鉴定新型、强效的逆转录酶抑制剂提供了独特而有用的工具。
• Dihydroalkoxybenzyloxopyrimidine (DABO) derivatives exhibiting spermicidal activity
  申请人：Parker Hughes Institute

  公开号：EP1557197A1

  公开（公告）日：2005-07-27

  Novel phenethyl-5-bromopyridylthiourea (PBT) and dihydroalkoxybenzyloxopyrimidine (DABO) derivatives exhibiting spermicidal activity as well as anti-viral activity. These novel compounds can be incorporated within contraceptive compositions to provide for spermicidal or sperm-immobilizing activity.

  新型苯乙基-5-溴吡啶硫脲（PBT）和二氢烷氧基苄氧基嘧啶（DABO）衍生物具有杀精活性和抗病毒活性。这些新型化合物可加入避孕药具中，以提供杀精或精子固定活性。
• Nonnucleoside inhibitors of reverse transcriptase, composite binding pocket and methods for use thereof
  申请人：Vig Rakesh

  公开号：US20050153995A1

  公开（公告）日：2005-07-14

  Novel compounds that are potent inhibitors of HIV reverse transcriptase (RT) are described in the invention. Thes novel compounds also inhibit replication of a retrovirus, such as human immunodeficiency virus-1 (HIV-1). The novel compounds of the invention include analogs and derivatives of phenethylthiazolylthiourea (PETT), of dihydroalkoxybenzyloxopyrimidine (DABO), and of 1-[( 2 -hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). The invention additionally provides a composite HIV reverse-transcriptase (RT) nonnucleoside inhibitor (NNI) binding pocket constructed from a composite of multiple NNI-RT complexes The composite RT-NNI binding pocket provides a unique and useful tool for designing and identifying novel, potent inhibitors of reverse transcriptase.

  本发明描述了对 HIV 逆转录酶（RT）具有强效抑制作用的新型化合物。这些新型化合物还能抑制逆转录病毒（如人类免疫缺陷病毒-1（HIV-1））的复制。本发明的新型化合物包括苯乙基噻唑基硫脲（PETT）、二氢烷氧基苄氧基嘧啶（DABO）和 1-[( 2 -羟乙氧甲基]-6-(苯硫基)胸腺嘧啶 (HEPT)。此外，本发明还提供了一种由多种 NNI-RT 复合物复合而成的复合 HIV 逆转录酶（RT）非核苷抑制剂（NNI）结合袋。这种复合 RT-NNI 结合袋为设计和鉴定新型、强效的逆转录酶抑制剂提供了一种独特而有用的工具。