(S)-9-(3-trityloxy-2-hydroxypropyl)-N⁶-trityladenine | 116142-81-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (S)-9-(3-trityloxy-2-hydroxypropyl)-N⁶-trityladenine
• 英文别名: (S)-1-(6-(tritylamino)-9H-purin-9-yl)-3-(trityloxy)propan-2-ol；9-(S)-[3-trityloxy-2-hydroxypropyl]-N⁶-trityladenine；N6,O3'-ditrityl-(S)-dihydroxypropyladenine；(s)-9-[3-Trityloxy-2-hydroxypropyl]-n6-trityladenine；(2S)-1-[6-(tritylamino)purin-9-yl]-3-trityloxypropan-2-ol
• CAS: 116142-81-5
• 化学式: C₄₆H₃₉N₅O₂
• 分子量: 693.848
• InChiKey: CEPWLQNPDAZEQB-RWYGWLOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  53
• 可旋转键数：
  13
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  85.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-9-(3-trityloxy-2-hydroxypropyl)-N⁶-trityladenine 生成 diethyl ((S)-1-(6-(tritylamino)-9H-purin-9-yl)-3-(trityloxy)propan-2-yloxy)methylphosphonate
  参考文献：
  名称：

  WEBB, ROBERT R. , II;MARTIN, JOHN C., TETRAHEDRON LETT., 28,(1987) N 42, 4963-4964

  摘要：

  DOI：
• 作为产物：
  描述：

  三苯甲基-(S)-缩水甘油醚 在 吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-9-(3-trityloxy-2-hydroxypropyl)-N⁶-trityladenine
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of Alkoxyalkyl Derivatives of 9-(S)-(3-Hydroxy-2-phosphonomethoxypropyl)adenine against Cytomegalovirus and Orthopoxviruses

  摘要：

  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.

  DOI：

  10.1021/jm050473m

文献信息

• 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。
• Acyclic nucleoside phosphonate diesters
  申请人：The Regents of the University of California, a California Corporation

  公开号：US08835630B1

  公开（公告）日：2014-09-16

  The present disclosure relates, inter alia, to compositions and methods for treating viral diseases and cancer. There are disclosed lipophilic antiviral and anticancer acyclic nucleoside phosphonate diesters, preparation thereof, and methods of using the compounds to treat viral diseases and cancer.

  本公开涉及，但不限于，用于治疗病毒性疾病和癌症的组合物和方法。公开了亲脂性抗病毒和抗癌无环核苷酸膦酸二酯，其制备方法，以及使用这些化合物治疗病毒性疾病和癌症的方法。
• Enantiomeric radiochemical synthesis of R and S (1-(6-amino-9H-purin-9-yl)-3-fluoropropan-2-yloxy)methylphosphonic acid (FPMPA)
  作者：Dale O. Kiesewetter、Kathleen Knudson、Matt Collins、Sharat Srinivasula、Esther Lim、Michele Di Mascio

  DOI：10.1002/jlcr.1505

  日期：2008.3.30

  Therapy for human immunodeficiency virus (HIV)-infected patients requires chronic multidrug administration. The eventual failure of therapy in some patients has brought into question the tissue concentration of the drugs. With an appropriately radiolabeled compound, we could utilize positron emission tomography to provide quantitative time–activity curves for various tissues. We have developed a fluorine-18 labeled analog of Tenofovir, the active metabolite of Tenofovir DF, a commonly prescribed component of multidrug therapy. Because (1-(6-amino-9H-purin-9-yl)-3-fluoropropan-2-yloxy)methylphosphonic acid (FPMPA) has a chiral center, we prepared both enantiomers and confirmed that the S-isomer exhibited significantly higher antiviral activity than the R-isomer. In viral replication inhibition assays in human MT4 cells infected with SHIVDH12R, S-FPMPA had an IC50 of 1.85 µM (95% CI; 0.8–5.53), while the R-isomer was inactive. An appropriate chiral precursor was prepared to allow the incorporation of fluorine-18. The [18F]FPMPA in racemic, R, or S form was prepared in a 50 min synthesis in 38±5% yield (n=23, corrected for decay). The product was of high radiochemical and enantiomeric purity. The specific activity of the final product was 4.0±1.8 Ci/µmol at EOB (end of bombardment). This product may provide information about drug tissue distribution in animal models under chronic drug treatment. Copyright © 2008 John Wiley & Sons, Ltd.

  针对感染人类免疫缺陷病毒（HIV）患者的治疗需要长期多药物联合管理。一些患者治疗最终失败的问题引发了人们对药物在组织中的浓度的质疑。通过合适的放射性标记化合物，我们可以利用正电子发射断层扫描（PET）为各种组织提供定量的时间—活动曲线。我们开发了一种氟-18标记的替诺福韦类似物，该类是替诺福韦DF的活性代谢物，替诺福韦DF是一种常用的多药物治疗成分。由于(1-(6-氨基-9H-嘌呤-9-基)-3-氟丙基-2-氧甲基)磷酸(FPMPA)具有手性中心，我们制备了两种对映异构体，并确认S-异构体的抗病毒活性显著高于R-异构体。在用SHIVDH12R感染的人MT4细胞的病毒复制抑制实验中，S-FPMPA的IC50为1.85 µM（95% CI；0.8–5.53），而R-异构体则无活性。我们制备了合适的手性前体，以便于氟-18的引入。[18F]FPMPA的外消旋体、R或S形式在38±5%的产率下进行了50分钟的合成（n=23，考虑衰变后修正）。该产品具有高放化学纯度和对映体纯度。最终产品的特定活性在轰击结束时为4.0±1.8 Ci/µmol。该产品可能为动物模型中的药物组织分布提供信息，尤其是在慢性药物治疗下。版权 © 2008 John Wiley & Sons, Ltd.
• Metabolically Stable Alkoxyalkyl Esters of Antiviral or Antiproliferative Phosphonates, Nucleoside Phosphonates and Nucleoside Phosphates
  申请人：Hostetler Y. Karl

  公开号：US20080009462A1

  公开（公告）日：2008-01-10

  The present invention relates to phosphonate, nucleoside phosphonate or nucleoside phosphate compounds, compositions containing them, processes for obtaining them, and their use in treating a variety of medical disorders, in particular viral infections, cancers and the like.

  本发明涉及磷酸酯、核苷酸磷酸酯或核苷酸磷酸盐化合物，包含它们的组合物，获得它们的过程以及它们在治疗各种医疗疾病，特别是病毒感染、癌症等方面的用途。
• [EN] METHODS FOR PREPARATION OF NUCLEOSIDE PHOSPHONATE ESTERS<br/>[FR] ELABORATION DE PHORPHONATES-ESTERS NUCLEOSIDIQUES
  申请人：UNIV CALIFORNIA

  公开号：WO2005087788A3

  公开（公告）日：2005-12-29