3-(oleyloxy)propyl toluenesulfonyloxymethylphosphonate sodium salt

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(oleyloxy)propyl toluenesulfonyloxymethylphosphonate sodium salt
• 英文别名: sodium;(4-methylphenyl)sulfonyloxymethyl-[3-[(Z)-octadec-9-enoxy]propoxy]phosphinate
• 化学式: C₂₉H₅₀O₇PS*Na
• 分子量: 596.741
• InChiKey: CYVQNWIMUXUTPL-GMFCBQQYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  4.68
• 重原子数：
  39
• 可旋转键数：
  25
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(oleyloxy)propyl toluenesulfonyloxymethylphosphonate sodium salt 在 sodium hydride 、 溶剂黄146 、 三乙胺 作用下， 生成 3-(oleyloxy)propyl (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine sodium salt
  参考文献：
  名称：

  Alkoxyalkyl Esters of ( S )-9-[3-Hydroxy-2-(Phosphonomethoxy)Propyl]Adenine Are Potent Inhibitors of the Replication of Wild-Type and Drug-Resistant Human Immunodeficiency Virus Type 1 In Vitro

  摘要：

  摘要 ( S )-9-[3-羟基-2-(磷酰甲氧基)丙基]腺嘌呤[( S )-HPMPA]是一种对多种 DNA 病毒有效的广谱抗病毒药物，但据报道对人类免疫缺陷病毒（HIV）无效。我们合成了几种(S)-HPMPA 的烷氧基烷基酯。 S )-HPMPA的几种烷氧基烷基酯，现在报告说，十六烷氧基丙基-( S )-HPMPA[HDP-( S )-HPMPA]和十八烷氧基乙基-( S )-HPMPA[ODE-( S )-HPMPA]的50%有效浓度为0.4至7.0纳摩尔，对具有逆转录酶突变M184V和K103N的HIV变体以及具有突变D67N、K70R、T215Y和K219Q的齐多夫定耐药变体几乎完全有效。对 HDP-( S )-HPMPA和ODE-( S )-HPMPA的耐药性。HDP-( S )-HPMPA对 1 型单纯疱疹病毒、人类巨细胞病毒、乙型肝炎病毒、腺病毒和正疱疹病毒也有活性，值得作为一种可能的艾滋病病毒感染疗法进行进一步评估。

  DOI：

  10.1128/aac.01223-05
• 作为产物：
  描述：

  3-oleyloxy-1-propanol 、 对甲苯磺酰氧甲基膦酸二乙酯 在 草酰氯 、 三甲基溴硅烷 作用下， 生成 3-(oleyloxy)propyl toluenesulfonyloxymethylphosphonate sodium salt
  参考文献：
  名称：

  Alkoxyalkyl Esters of ( S )-9-[3-Hydroxy-2-(Phosphonomethoxy)Propyl]Adenine Are Potent Inhibitors of the Replication of Wild-Type and Drug-Resistant Human Immunodeficiency Virus Type 1 In Vitro

  摘要：

  摘要 ( S )-9-[3-羟基-2-(磷酰甲氧基)丙基]腺嘌呤[( S )-HPMPA]是一种对多种 DNA 病毒有效的广谱抗病毒药物，但据报道对人类免疫缺陷病毒（HIV）无效。我们合成了几种(S)-HPMPA 的烷氧基烷基酯。 S )-HPMPA的几种烷氧基烷基酯，现在报告说，十六烷氧基丙基-( S )-HPMPA[HDP-( S )-HPMPA]和十八烷氧基乙基-( S )-HPMPA[ODE-( S )-HPMPA]的50%有效浓度为0.4至7.0纳摩尔，对具有逆转录酶突变M184V和K103N的HIV变体以及具有突变D67N、K70R、T215Y和K219Q的齐多夫定耐药变体几乎完全有效。对 HDP-( S )-HPMPA和ODE-( S )-HPMPA的耐药性。HDP-( S )-HPMPA对 1 型单纯疱疹病毒、人类巨细胞病毒、乙型肝炎病毒、腺病毒和正疱疹病毒也有活性，值得作为一种可能的艾滋病病毒感染疗法进行进一步评估。

  DOI：

  10.1128/aac.01223-05

文献信息

• Synthesis and Antiviral Evaluation of Alkoxyalkyl Derivatives of 9-(<i>S</i>)-(3-Hydroxy-2-phosphonomethoxypropyl)adenine against Cytomegalovirus and Orthopoxviruses
  作者：James R. Beadle、William B. Wan、Stephanie L. Ciesla、Kathy A. Keith、Caroll Hartline、Earl R. Kern、Karl Y. Hostetler

  DOI：10.1021/jm050473m

  日期：2006.3.1

  9-(S)-(3-Hydroxy-2-phosphonomethoxypropyl)adenine [(S)-HPMPA] was one of the first acyclic nucleoside phosphonates described and has been reported to have good antiviral activity against most double-stranded DNA viruses, including the herpes group viruses and the orthopoxviruses. However, (S)-HPMPA is not orally bioavailable and has not been developed for clinical use. We have prepared orally bioavailable lipid esters of (S)-HPMPA and report their synthesis and antiviral evaluation against cytomegalovirus and orthopoxviruses. These esters were evaluated in vitro in cells infected with human cytomegalovirus (HCMV), murine cytomegalovirus (MCMV), vaccinia (VV), and cowpox viruses (CV). The most active compound, oleyloxyethyl-(S)-HPMPA, was found to have EC50 value of 0.003 mu M against HCMV vs 1.4 mu M for unmodified HPMPA. In cells infected with VV and CV, octadecyloxyethyl-(S)-HPMPA had EC50 values of 0.01-0.02 mu M versus 2.7 -4.0 mu M for unmodified HPMPA. When compared with the alkoxyalkyl esters of cidofovir, the corresponding alkoxyalkyl esters of (S)-HPMPA were equally active against HCMV and MCMV but were 15-20-fold more active against VV and CV in vitro. The alkoxyalkyl esters of (S)-HPMPA are promising new compounds worthy of further investigation for treatment of infections caused by herpes viruses and orthopoxviruses.
• Alkoxyalkyl Esters of ( <i>S</i> )-9-[3-Hydroxy-2-(Phosphonomethoxy)Propyl]Adenine Are Potent Inhibitors of the Replication of Wild-Type and Drug-Resistant Human Immunodeficiency Virus Type 1 In Vitro
  作者：Karl Y. Hostetler、Kathy A. Aldern、William B. Wan、Stephanie L. Ciesla、James R. Beadle

  DOI：10.1128/aac.01223-05

  日期：2006.8

  ( S )-9-[3-Hydroxy-2-(phosphonomethoxy)propyl]adenine [( S )-HPMPA], is an effective broad-spectrum antiviral against many DNA viruses but has been reported to be inactive against human immunodeficiency virus (HIV). We synthesized several alkoxyalkyl esters of ( S )-HPMPA and now report that hexadecyloxypropyl-( S )-HPMPA [HDP-( S )-HPMPA] and octadecyloxyethyl-( S )-HPMPA [ODE-( S )-HPMPA]had 50% effective concentrations of 0.4 to 7.0 nanomolar and were nearly fully active against HIV variants having reverse transcriptase mutations M184V and K103N and against a zidovudine-resistant variant with mutations D67N, K70R, T215Y, and K219Q. Resistance to HDP-( S )-HPMPA and ODE-( S )-HPMPA was noted for a mutant with mutation K65R. HDP-( S )-HPMPA is also active against herpes simplex virus type 1, human cytomegalovirus, hepatitis B virus, adenoviruses, and orthopoxviruses and is worthy of further evaluation as a possibly therapy for HIV infection.

  摘要 ( S )-9-[3-羟基-2-(磷酰甲氧基)丙基]腺嘌呤[( S )-HPMPA]是一种对多种 DNA 病毒有效的广谱抗病毒药物，但据报道对人类免疫缺陷病毒（HIV）无效。我们合成了几种(S)-HPMPA 的烷氧基烷基酯。 S )-HPMPA的几种烷氧基烷基酯，现在报告说，十六烷氧基丙基-( S )-HPMPA[HDP-( S )-HPMPA]和十八烷氧基乙基-( S )-HPMPA[ODE-( S )-HPMPA]的50%有效浓度为0.4至7.0纳摩尔，对具有逆转录酶突变M184V和K103N的HIV变体以及具有突变D67N、K70R、T215Y和K219Q的齐多夫定耐药变体几乎完全有效。对 HDP-( S )-HPMPA和ODE-( S )-HPMPA的耐药性。HDP-( S )-HPMPA对 1 型单纯疱疹病毒、人类巨细胞病毒、乙型肝炎病毒、腺病毒和正疱疹病毒也有活性，值得作为一种可能的艾滋病病毒感染疗法进行进一步评估。