2-cyclopenlythio-6-(2,6-diflurophenymethyl)-3,4-dihydro-5-methylpyrimidin-4-(3H)-one

• 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-cyclopenlythio-6-(2,6-diflurophenymethyl)-3,4-dihydro-5-methylpyrimidin-4-(3H)-one
• 英文别名: 2-cyclopentylsulfanyl-4-[(2,6-difluorophenyl)methyl]-5-methyl-1H-pyrimidin-6-one
• 化学式: C₁₇H₁₈F₂N₂OS
• 分子量: 336.406
• InChiKey: JDNVZVKHBJZAPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,6-二氟苯乙酸 在 sodium ethanolate 、 potassium carbonate 、 三乙胺 、 magnesium chloride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 33.0h， 生成 2-cyclopenlythio-6-(2,6-diflurophenymethyl)-3,4-dihydro-5-methylpyrimidin-4-(3H)-one
  参考文献：
  名称：

  5-Alkyl-2-(alkylthio)-6-(2,6-dihalophenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones:  Novel Potent and Selective Dihydro-alkoxy-benzyl-oxopyrimidine Derivatives

  摘要：

  Molecular modeling analysis of compounds belonging to the recently published series of dihydroalkoxy-benzyl-oxopyrimidines (DABOs), such as S-DABOs and DATNOs, gave support to the design of new 2,6-disubstituted benzyl-DABO derivatives as highly potent and specific inhibitors of the HIV-1 reverse transcriptase (RT). To follow up on the novel DABO derivatives, we decided to investigate the effect of electron-withdrawing substituents in the benzyl unit of the S-DABO skeleton versus their anti-HIV-1 activity. Such chemical modifications impacted the inhibitory activity, especially when two halogen units were introduced at positions 2 and 6 in the phenyl portion of the benzyl group bound to C-6 of the pyrimidine ring. Various 5-alkyl-2-(alkyl(or cycloalkyl)thio)-6-(2,B-dichloro(or 2, 6-difluoro)phenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones were then synthesized and tested as anti-HIV-1 agents in both cell-based and enzyme (recombinant reverse transcriptase, rRT) assays. Among the various mono- and disubstituted phenyl derivatives, the most potent were those containing a 6-(2,6-difluorophenylmethyl) substituent (F-DABOs), which showed EC50's ranging between 40 and 90 nM and selectivity indexes up to greater than or equal to 5000. An excellent correlation was found between EC50 and IC50 values which confirmed that these compounds act as inhibitors of the HIV-1 RT. The structure-activity relationships of the newly synthesized pyrimidinones are presented herein.

  DOI：

  10.1021/jm980260f

文献信息

• Methods for inhibiting the transmission of HIV using topically applied substituted 6-benzyl-4-oxopyrimidines
  申请人：——

  公开号：US20030008887A1

  公开（公告）日：2003-01-09

  A method for inhibiting sexual transmission of HIV comprising topically applying to the skin or epithelial tissue of a human a composition comprising a non-nucleoside reverse transcriptase inhibitor (“NNRTI”) that is able to inhibit viral replication for periods exceeding 12, 24, or even 36 days, at concentrations below even 10 &mgr;M. In one embodiment the NNRTI is a dihydro-alkyloxy-benzyl-oxopyrimidine (DABO).

  一种抑制HIV性传播的方法，包括将一种含有非核苷类反转录酶抑制剂（“NNRTI”）的组合物局部涂抹于人体的皮肤或上皮组织上，该NNRTI能够在浓度低于10 &mgr;M的情况下抑制病毒复制，持续时间超过12、24或36天。在一种实施方式中，NNRTI是一种二氢烷氧基苯基嘧啶（DABO）。
• Methods for inhibiting the transmission of HIV using topically applied substituted 6-benzyl-4- oxopyrimidines
  申请人：Idenix Pharmaceuticals, Inc.

  公开号：US20030225114A1

  公开（公告）日：2003-12-04

  A method for inhibiting sexual transmission of HIV comprising topically applying to the skin or epithelial tissue of a human a composition comprising a non-nucleoside reverse transcriptase inhibitor (“NNRTI”) that is able to inhibit viral replication for periods exceeding 12, 24, or even 36 days, at concentrations below even 10 &mgr;M. In one embodiment the NNRTI is a dihydro-alkyloxy-benzyl-oxopyrimidine (DABO).

  一种抑制艾滋病毒性传播的方法，包括在人的皮肤或上皮组织局部施用一种组合物，该组合物包含一种非核苷类逆转录酶抑制剂（"NNRTI"），它能够抑制病毒复制超过 12、24 或甚至 36 天，浓度甚至低于 10 &mgr;M。在一个实施方案中，NNRTI 是一种二氢-烷氧基-苄基-氧代嘧啶（DABO）。
• Substituted 6-benzyl-4-oxopyrimidines, process for their preparation and pharmaceutical compositions containing them
  申请人：——

  公开号：US20040092539A1

  公开（公告）日：2004-05-13

  The invention concerns novel substituted 6-benzyl-4-oxopyrimnidines of general formula (A). These compounds inhibit reverse transcriptase encoded by human immunodeficiency virus (HIV) or pharmaceutically acceptable salts thereof, and find their application in the prevention and treatment of HIV infection and the treatment of the resulting acquired immune deficiency syndrome (AIDS). Pharmaceutical compositions containing the compounds and a method of use of the present compounds and other agents for the treatment of AIDS and viral infection by HIV are also envisaged. 1

  本发明涉及通式（A）的新型取代 6-苄基-4-氧代嘧啶。这些化合物可抑制由人类免疫缺陷病毒（HIV）编码的逆转录酶或其药学上可接受的盐类，可用于预防和治疗 HIV 感染以及治疗由此引起的获得性免疫缺陷综合征（AIDS）。还设想了含有本发明化合物的药物组合物以及本发明化合物和其他制剂治疗艾滋病和 HIV 病毒感染的使用方法。 1
• METHODS FOR INHIBITING THE TRANSMISSION OF HIV USING TOPICALLY APPLIED SUBSTITUTED 6-BENZYL-4-OXOPYRIMIDINES
  申请人：Idenix (Cayman) Limited

  公开号：EP1343502A2

  公开（公告）日：2003-09-17
• US6545007B2
  申请人：——

  公开号：US6545007B2

  公开（公告）日：2003-04-08