dimethyl 3-(1,3-dibenzyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3,3-ethylenedioxy-1-hydroxypropylphosphonate | 934365-26-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: dimethyl 3-(1,3-dibenzyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3,3-ethylenedioxy-1-hydroxypropylphosphonate
• 英文别名: 1,3-Dibenzyl-5-[2-(2-dimethoxyphosphoryl-2-hydroxyethyl)-1,3-dioxolan-2-yl]pyrimidine-2,4-dione；1,3-dibenzyl-5-[2-(2-dimethoxyphosphoryl-2-hydroxyethyl)-1,3-dioxolan-2-yl]pyrimidine-2,4-dione
• CAS: 934365-26-1
• 化学式: C₂₅H₂₉N₂O₈P
• 分子量: 516.488
• InChiKey: MULUCVFCRLZLPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  dimethyl 3-(1,3-dibenzyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3,3-ethylenedioxy-1-hydroxypropylphosphonate 在 4-甲基苯磺酸吡啶 水 作用下， 以 丙酮 为溶剂， 以65%的产率得到dimethyl 3-(1,3-dibenzyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1-hydroxy-3-oxopropylphosphonate
  参考文献：
  名称：

  A novel diketo phosphonic acid that exhibits specific, strand-transfer inhibition of HIV integrase and anti-HIV activity

  摘要：

  We have synthesized novel phosphonic acid analogues of P-diketo acids. Interestingly, the phosphonic acid isostere, 2, of our anti-HIV compound, 1, was an inhibitor of only the strand transfer step, in stark contrast to 1. Compound 2 had lower anti-HIV activity than 1, but was more active and less toxic than the phosphonic acid analogue of L-708906. These isosteric compounds represent the first examples of beta-diketo phosphonic acids of structural, synthetic, and antiviral interest. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.009
• 作为产物：
  描述：

  5-甲酰基尿嘧啶 在 4-甲基苯磺酸吡啶 二异丁基氢化铝 、 potassium carbonate 、 三乙胺 、 原甲酸三乙酯 、 tin(ll) chloride 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 dimethyl 3-(1,3-dibenzyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3,3-ethylenedioxy-1-hydroxypropylphosphonate
  参考文献：
  名称：

  A novel diketo phosphonic acid that exhibits specific, strand-transfer inhibition of HIV integrase and anti-HIV activity

  摘要：

  We have synthesized novel phosphonic acid analogues of P-diketo acids. Interestingly, the phosphonic acid isostere, 2, of our anti-HIV compound, 1, was an inhibitor of only the strand transfer step, in stark contrast to 1. Compound 2 had lower anti-HIV activity than 1, but was more active and less toxic than the phosphonic acid analogue of L-708906. These isosteric compounds represent the first examples of beta-diketo phosphonic acids of structural, synthetic, and antiviral interest. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.009

文献信息

• WO2007/106450
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] DIKETO ACIDS WITH NUCLEOBASE SCAFFOLDS: ANTI-HIV REPLICATION INHIBITORS TARGETED AT HIV INTEGRASE IN COMBINATION THERAPY<br/>[FR] ACIDES DICETO A SQUELETTES NUCLEOBASE : INHIBITEURS DE REPLICATION ANTI-VIH CIBLES AU NIVEAU DE L'INTEGRASE DU VIH EN THERAPIE DE COMBINAISON
  申请人：UNIV GEORGIA RES FOUND

  公开号：WO2007106450A2

  公开（公告）日：2007-09-20

  [EN] A new class of diketo acids constructed on nucleobase scaffolds, designed as inhibitors of HIV replication through inhibition of HIV integrase, is described. These compounds are useful in the prevention or treatment of infection by HFV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents, especially other anti-HIV compounds (including other anti-HIV integrase agents), which can be used to create combination anti- HIV cocktails as disclosed herein. Methods of treating AIDS and ARC and methods of treating or preventing infection by HIV are also described. Compounds of the present application include those of formula I and include tautomers, regioisomers, geometric isomers, and where applicable, optical isomers thereof, and pharmaceutically acceptable salts thereof, wherein the nucleobase scaffold and R groups are as otherwise defined in the specification. These are combined with any number of typical other anti-HIV agents to provide an effective treatment modality for HIV infections, including AIDS and ARC.
  [FR] La présente invention concerne une nouvelle classe d'acides dicéto construite sur des squelettes de nucléobase, conçus comme inhibiteurs de réplication VIH par l'inhibition de l'intégrase du VIH. Ces composés sont utiles dans la prévention ou le traitement d'une infection par HFV et dans le traitement du SIDA et du para-sida (ARC), soit en tant que composés ou sels pharmaceutiquement acceptables, avec des supports pharmaceutiquement acceptables, en combinaison avec des agents antiviraux, immunomodulateurs, antibiotiques, vaccins et autres agents thérapeutiques, particulièrement d'autres composés anti-VIH (y compris d'autres agents de l'intégrase anti-VIH) qui peuvent être utilisés pour créer des cocktails de combinaison anti-VIH comme indiqué ici. Des procédés de traitement du SIDA et de l'ARC et des procédés de traitement ou de prévention d'une infection par le VIH sont également décrits. Citons parmi les composés de la présente application, ceux de formule I et des tautomères, régioisomères, isomères géométriques et, le cas échéant, des isomères optiques dérivés et des sels pharmaceutiquement acceptables, sachant que le squelette de nucléobase et les groupes R sont tels qu'autrement définis dans la spécification. Ils sont combinés avec tout un ensemble d'autres agents anti-VIH typiques afin de fournir une modalité de traitement efficace des infections HIV, y compris le SIDA et le para-sida.
• A novel diketo phosphonic acid that exhibits specific, strand-transfer inhibition of HIV integrase and anti-HIV activity
  作者：Guochen Chi、Vasu Nair、Elena Semenova、Yves Pommier

  DOI：10.1016/j.bmcl.2006.12.009

  日期：2007.3

  We have synthesized novel phosphonic acid analogues of P-diketo acids. Interestingly, the phosphonic acid isostere, 2, of our anti-HIV compound, 1, was an inhibitor of only the strand transfer step, in stark contrast to 1. Compound 2 had lower anti-HIV activity than 1, but was more active and less toxic than the phosphonic acid analogue of L-708906. These isosteric compounds represent the first examples of beta-diketo phosphonic acids of structural, synthetic, and antiviral interest. (c) 2006 Elsevier Ltd. All rights reserved.