(R)-2-O-<(diisopropylphosphono)methoxy>-1-O-(methylsulfonyl)-1,2-propanediol | 138247-64-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: (R)-2-O-<(diisopropylphosphono)methoxy>-1-O-(methylsulfonyl)-1,2-propanediol
• 英文别名: (R)-2-O-<(diisopropylphosphono)methyl>-1-O-(methylsulfonyl)-1,2-propanediol；(S)-2-O-[(diisopropylphosphono)methyl]-1-O-methanesulfonyl-1,2-propanediol；[(2S)-2-[di(propan-2-yloxy)phosphorylmethoxy]propyl] methanesulfonate
• CAS: 138247-64-0
• 化学式: C₁₁H₂₅O₇PS
• 分子量: 332.355
• InChiKey: ZVEBNAPRNYFGBE-NSHDSACASA-N

物化性质

• 沸点：
  438.4±30.0 °C(Predicted)
• 密度：
  1.179±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  20
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  96.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-2-O-<(diisopropylphosphono)methoxy>-1-O-(methylsulfonyl)-1,2-propanediol 在 palladium on activated charcoal sodium azide 、 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、275.79 kPa 条件下， 反应 13.5h， 生成 (R)-<2-<(diisopropylphosphono)methoxy>propyl>amine
  参考文献：
  名称：

  Synthesis and Antiviral Activity of 8-Aza Analogs of Chiral [2-(Phosphonomethoxy)propyl]guanines

  摘要：

  (R)- And (S)-8-aza-9-[2-(phosphonomethoxy)propyl] [(R)- and (S)-8-aza-PMPG] were synthesized and tested in vitro for anti-human immunodeficiency virus (HIV) activity. The synthesis of the above compounds and of (R)-9-[2-(phosphonomethoxy)propyl]guanine [(R)-PMPG] was carried out through the alkylation of 8-azaguanine or guanine with (R)- and (S)2-O-[(diisopropylphosphono)methyl]-1-O-(followed by deprotection of the phosphonic moiety. A different, even more convenient synthesis of (R)-8-aza-PMPG starting from 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone and (R)-[2-[(diisopropylphosphono)methoxy]propyl]amine is also reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV activity in the MTT assay with EC(50) values of 12 and 4.5 mu M, respectively. The corresponding S enantiomers were found to be less potent. When evaluated in combination with AZT, ddI, or DABO 603, (R)-8-aza-PMPG gave additive, additive, and synergistic anti-HIV-1 effects, respectively.

  DOI：

  10.1021/jm00020a015
• 作为产物：
  描述：

  (二异丙氧基磷酰)甲基对甲苯磺酸酯 在 camphor-10-sulfonic acid 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 31.0h， 生成 (R)-2-O-<(diisopropylphosphono)methoxy>-1-O-(methylsulfonyl)-1,2-propanediol
  参考文献：
  名称：

  9- [2-（膦酰基甲氧基）乙基]鸟嘌呤的甲基衍生物的合成及抗病毒活性。

  摘要：

  已经合成了许多9- [2-（膦甲氧基）乙基]鸟嘌呤的甲基衍生物（PMEG，1），并在体外测试了其抗疱疹和抗人免疫缺陷病毒（HIV）的活性。在这些类似物中，（R）-2'-甲基-PMEG [[R] -3]和2'，2'-二甲基-PMEG（7）在XTT分析中显示出有效的抗HIV活性，EC50值为1.0和分别为2.6 microM。发现相应的（S）-2'-甲基-PMEG [（S）-3]对HIV的效力较低。另外，制备9- [3-羟基-2-（膦甲氧基）丙基]鸟嘌呤的（R）和（S）对映异构体（HPMPG，8）用于比较生物学活性，并显示出对疱疹病毒的活性和等效性。 ，但对HIV无效。

  DOI：

  10.1021/jm00094a005

文献信息

• Use of chiral 2-(phosphonomethoxy)propyl guanines as antiviral agents
  申请人：Institute of Organic Chemistry and Biochemistry of the Academy of

  公开号：US05302585A1

  公开（公告）日：1994-04-12

  The present invention provides chiral nucleotide analogs having the Formulas I and II ##STR1## and pharmaceutically acceptable salts and solvates thereof, and their pharmaceutical compositions for use in the treatment of viral infections, especially those caused by human immunodeficiency virus (HIV).

  本发明提供了具有以下式I和II的手性核苷酸类似物，以及其药用可接受的盐和溶剂化物，以及它们的药用组合物，用于治疗病毒感染，特别是由人类免疫缺陷病毒（HIV）引起的感染。
• Chiral 2-(phosphonomethoxy)propyl guanines as antiviral agents
  申请人：INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY OF THE ACADEMY OF SCIENCES OF THE CZECH REPUBLIC

  公开号：EP0452935A1

  公开（公告）日：1991-10-23

  The present invention provides a chiral nucleotide analog having the Formula I which is substantially free of the (S)-isomer and pharmaceutically acceptable salts and solvates thereof, and their pharmaceutical compositions, which is useful in the treatment of viral infections, especially those caused by human immunodeficiency virus (HIV).

  本发明提供了一种具有式 I 的手性核苷酸类似物 的手性核苷酸类似物、其药学上可接受的盐和溶剂及其药物组合物，可用于治疗病毒感染，尤其是由人类免疫缺陷病毒（HIV）引起的病毒感染。
• US5302585A
  申请人：——

  公开号：US5302585A

  公开（公告）日：1994-04-12
• Synthesis and antiviral activity of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine
  作者：Kuo Long Yu、Joanne J. Bronson、Hyekyung Yang、Amy Patick、Masud Alam、Vera Brankovan、Roelf Datema、Michael J. M. Hitchcock、John C. Martin

  DOI：10.1021/jm00094a005

  日期：1992.8

  A number of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG, 1) have been synthesized and tested in vitro for anti-herpes and anti-human immunodeficiency virus (HIV) activity. Among these analogues, (R)-2'-methyl-PMEG [(R)-3] and 2',2'-dimethyl-PMEG (7) demonstrated potent anti-HIV activity in the XTT assay with EC50 values of 1.0 and 2.6 microM, respectively. The corresponding (S)-2'-methyl-PMEG

  已经合成了许多9- [2-（膦甲氧基）乙基]鸟嘌呤的甲基衍生物（PMEG，1），并在体外测试了其抗疱疹和抗人免疫缺陷病毒（HIV）的活性。在这些类似物中，（R）-2'-甲基-PMEG [[R] -3]和2'，2'-二甲基-PMEG（7）在XTT分析中显示出有效的抗HIV活性，EC50值为1.0和分别为2.6 microM。发现相应的（S）-2'-甲基-PMEG [（S）-3]对HIV的效力较低。另外，制备9- [3-羟基-2-（膦甲氧基）丙基]鸟嘌呤的（R）和（S）对映异构体（HPMPG，8）用于比较生物学活性，并显示出对疱疹病毒的活性和等效性。 ，但对HIV无效。
• Synthesis and Antiviral Activity of 8-Aza Analogs of Chiral [2-(Phosphonomethoxy)propyl]guanines
  作者：Palmarisa Franchetti、Ghassan Abu Sheikha、Loredana Cappellacci、Mario Grifantini、Antonella De Montis、Giovanna Piras、Anna Giulia Loi、Paolo La Colla

  DOI：10.1021/jm00020a015

  日期：1995.9

  (R)- And (S)-8-aza-9-[2-(phosphonomethoxy)propyl] [(R)- and (S)-8-aza-PMPG] were synthesized and tested in vitro for anti-human immunodeficiency virus (HIV) activity. The synthesis of the above compounds and of (R)-9-[2-(phosphonomethoxy)propyl]guanine [(R)-PMPG] was carried out through the alkylation of 8-azaguanine or guanine with (R)- and (S)2-O-[(diisopropylphosphono)methyl]-1-O-(followed by deprotection of the phosphonic moiety. A different, even more convenient synthesis of (R)-8-aza-PMPG starting from 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone and (R)-[2-[(diisopropylphosphono)methoxy]propyl]amine is also reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV activity in the MTT assay with EC(50) values of 12 and 4.5 mu M, respectively. The corresponding S enantiomers were found to be less potent. When evaluated in combination with AZT, ddI, or DABO 603, (R)-8-aza-PMPG gave additive, additive, and synergistic anti-HIV-1 effects, respectively.