4-(methylsulfonyl)phenyl phosphorodichloridate | 125440-36-0

• 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: 4-(methylsulfonyl)phenyl phosphorodichloridate
• 英文别名: 4-(methylsulphonyl)phenyl phosphorodichloridate；1-Dichlorophosphoryloxy-4-methylsulfonylbenzene
• CAS: 125440-36-0
• 化学式: C₇H₇Cl₂O₄PS
• 分子量: 289.076
• InChiKey: FKQVBUIGFXQQPU-UHFFFAOYSA-N

物化性质

• 沸点：
  185 °C(Press: 1 Torr)
• 密度：
  1.557±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  68.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(methylsulfonyl)phenyl phosphorodichloridate 、 2',3'-双脱氧腺苷 在 吡啶 、 N-甲基咪唑 作用下， 生成 4-(Methylsulphonyl)phenyl bis(2',3'-dideoxyadenosin-5'-yl) phosphate
  参考文献：
  名称：

  Antiviral compounds

  摘要：

  公式I的化合物或其药学上可接受的盐：其中公式中R1代表脂肪族烃基；Ar代表取代或未取代的芳香族核；X代表--SO2--或--CO--，而R2和R3可能相同或不同，代表公式(a)、(b)、(c)、(d)、(e)、(f)、(g)、(h)或(i)的基团：其中B代表公式(A)、(G)、(C)、(H)或(T)的核苷酸碱基残基：但当R2和R3都代表公式(a)的未取代基团时，B代表公式(A)、(G)、(C)或(H)的核苷酸碱基残基，以其抗病毒活性而获得价值。

  公开号：

  US05585364A1
• 作为产物：
  描述：

  4-(甲硫基)苯酚 在 N-甲基咪唑 、 sodium periodate 、 三氯氧磷 作用下， 以 甲醇 、 水 为溶剂， 反应 86.0h， 生成 4-(methylsulfonyl)phenyl phosphorodichloridate
  参考文献：
  名称：

  Synthesis and biological properties of novel phosphotriesters: a new approach to the introduction of biologically active nucleotides into cells

  摘要：

  A series of aryl bis(3'-O-acetylthymidin-5'-yl) phosphate derivatives have been synthesized in order to find a suitable aryl derivative which would hydrolyze to the bis(nucleosid-5'-yl) phosphate under physiological conditions. The 4-(methylsulfonyl)phenyl derivative was selected and 4-(methylsulfonyl)phenyl bis[(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl] phosphate (6d) and bis[2-(guanin-9-ylmethoxy)ethoxy]-4-(methylsulfonyl)phenyl phosphate (7b) were prepared. The former compound (6d) was stable in human serum and only following hydrolysis to the 5'-5'-linked diester (half-life of 17 h at pH 7.7) was it enzymatically degraded very rapidly by phosphodiesterases. Compounds 6d and 7b were evaluated for antiherpesvirus effects, both in vitro and in vivo. Their antiviral spectrum and potency was remarkably similar to that of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 9-[(2-hydroxyethoxy)-methyl]guanine (ACV), suggesting that they only act as prodrugs of BVDU and ACV, respectively. However, compound 6d did show unexpected toxicity, which could be explained by the liberation of BVDUMP following penetration of the triester into the cell.

  DOI：

  10.1021/jm00167a019

文献信息

• FARROW, STUART N.;JONES, A. STANLEY;KUMAR, AJIT;WALKER, RICHARD T.;BALZAR+, J. MED. CHEM., 33,(1990) N, C. 1400-1406
  作者：FARROW, STUART N.、JONES, A. STANLEY、KUMAR, AJIT、WALKER, RICHARD T.、BALZAR+

  DOI：——

  日期：——
• WALKER, RICHARD THOMAS;JONES, ALBERT STANLEY
  作者：WALKER, RICHARD THOMAS、JONES, ALBERT STANLEY

  DOI：——

  日期：——
• US5585364A
  申请人：——

  公开号：US5585364A

  公开（公告）日：1996-12-17
• [EN] ANTIVIRAL COMPOUNDS
  申请人：WALKER, Richard, Thomas

  公开号：WO1990012023A1

  公开（公告）日：1990-10-18

  (EN) Compounds of formula (I) or a pharmaceutically acceptable salt thereof, in which R1 represents an aliphatic hydrocarbyl group; Ar represents a substituted or unsubstituted aromatic nucleus; X represents -SO2- or -CO- and R2 and R3 which may be identical or different represent moieties of formula (a), (b), (c), (d), (e), (f), (g), (h) or (i), wherein B represents the residue of a nucleoside base of formula (A), (G), (C), (H) or (T), provided that when R2 and R3 both represent an unsubstituted moiety of formula (a), B represents the residue of a nucleoside base which is of formula (A), (G), (C) or (H) are of value for their antiviral activity.(FR) Composés de formule (I) ou sel d'un tel composé pharmaceutiquement acceptable dans laquelle R1 représente un groupe hydrocarbyle aliphatique; Ar représente un noyau aromatique substitué ou non; X représente -SO2- ou -CO- et R2 et R3 identiques ou différents représentent des unités de formule (a), (b), (c), (d), (e), (f), (g), (h) ou (i), où B représente le résidu d'une base nucléoside de formule (A), (G), (C), (H) ou (T), à condition que lorsque R2 et R3 représentent tous les deux une unité non substituée de formule (a) B représente le résidu d'une base nucléoside de formule (A), (G), (C) ou (H). Lesdits composés sont utiles en raison de leur action antivirale.
• Synthesis and biological properties of novel phosphotriesters: a new approach to the introduction of biologically active nucleotides into cells
  作者：Stuart N. Farrow、A. Stanley Jones、Ajit Kumar、Richard T. Walker、Jan Balzarini、Erik De Clercq

  DOI：10.1021/jm00167a019

  日期：1990.5

  A series of aryl bis(3'-O-acetylthymidin-5'-yl) phosphate derivatives have been synthesized in order to find a suitable aryl derivative which would hydrolyze to the bis(nucleosid-5'-yl) phosphate under physiological conditions. The 4-(methylsulfonyl)phenyl derivative was selected and 4-(methylsulfonyl)phenyl bis[(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl] phosphate (6d) and bis[2-(guanin-9-ylmethoxy)ethoxy]-4-(methylsulfonyl)phenyl phosphate (7b) were prepared. The former compound (6d) was stable in human serum and only following hydrolysis to the 5'-5'-linked diester (half-life of 17 h at pH 7.7) was it enzymatically degraded very rapidly by phosphodiesterases. Compounds 6d and 7b were evaluated for antiherpesvirus effects, both in vitro and in vivo. Their antiviral spectrum and potency was remarkably similar to that of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 9-[(2-hydroxyethoxy)-methyl]guanine (ACV), suggesting that they only act as prodrugs of BVDU and ACV, respectively. However, compound 6d did show unexpected toxicity, which could be explained by the liberation of BVDUMP following penetration of the triester into the cell.