2-chloro-8-(2-chloro-4H-1,3,2-benzodioxaphosphinin-8-yl)-4H-1,3,2-benzodioxaphosphinine | 935681-38-2

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 2-chloro-8-(2-chloro-4H-1,3,2-benzodioxaphosphinin-8-yl)-4H-1,3,2-benzodioxaphosphinine
• CAS: 935681-38-2
• 化学式: C₁₄H₁₀Cl₂O₄P₂
• 分子量: 375.085
• InChiKey: YOMUNKVCTPWROU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-8-(2-chloro-4H-1,3,2-benzodioxaphosphinin-8-yl)-4H-1,3,2-benzodioxaphosphinine 在 叔丁基过氧化氢 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 生成 5-methyl-1-[(2R,5S)-5-[[8-[2-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinin-8-yl]-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinin-2-yl]oxymethyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4-dione
  参考文献：
  名称：

  NOVEL CYCLOSAL NUCLEOTIDES WITH REDUCED INHIBITORY POTENCY TOWARD HUMAN BUTYRYLCHOLINESTERASE

  摘要：

  Two novel cycloSal-d4T monophosphates (d4TMPs) with increased steric demand have been synthesized via a new synthetic route. While 3-cyclohexyl-cycloSal d4TMP did not show a significantly reduced inhibitory potency toward human butrylylcholinesterase, the opposite was the case for the second novel pronucleotide, bi-(cycloSal-d4TMP).

  DOI：

  10.1081/ncn-200061791
• 作为产物：
  描述：

  2,2'-二羟基联苯 在 盐酸 、 lithium aluminium tetrahydride 、 正丁基锂 、 sodium hydride 、 三氯化磷 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 43.17h， 生成 2-chloro-8-(2-chloro-4H-1,3,2-benzodioxaphosphinin-8-yl)-4H-1,3,2-benzodioxaphosphinine
  参考文献：
  名称：

  Bis-cycloSal-d4T-monophosphates:  Drugs That Deliver Two Molecules of Bioactive Nucleotides

  摘要：

  Bis-cycloSal-d4T-monophosphates have been synthesized as potentially anti-HIV active "dimeric" prodrugs of 2',3'-dideoxy-2',3'-didehydrothymidine monophosphate (d4TMP). These pronucleotides display a mask-drug ratio of 1:2, a novelty in the field of pronucleotides. Both bis-cycloSal-d4TMP 6 and bis-5-methyl-cycloSal-d4TMP 7 showed increased hydrolytic stability as compared to their "monomeric" counterparts and a completely selective hydrolytic release of d4TMP. The hydrolysis pathway was investigated via P-31 NMR spectroscopy. Moreover, due to the steric bulkiness, compound 6 already displayed strongly reduced inhibitor potency toward human butyrylcholinesterase (BChE), while compound 7 turned out to be devoid of any inhibitory activity against BChE. Partial separation of the diastereomeric mixture of 6 revealed strong dependence of the pronucleotides' properties on the stereochemistry at the phosphorus centers. Both 6and 7 showed good activity against HIV-1 and HIV-2 in wild-type CEM cells in vitro. These compounds were significantly more potent than the parent nucleoside d4T 1in HIV-2-infected TK-deficient CEM cells, indicating an efficient TK-bypass.

  DOI：

  10.1021/jm0611713

文献信息

• Bis-<i>cyclo</i>Sal-d4T-monophosphates:  Drugs That Deliver Two Molecules of Bioactive Nucleotides
  作者：Christian Ducho、Ulf Görbig、Sönke Jessel、Nicolas Gisch、Jan Balzarini、Chris Meier

  DOI：10.1021/jm0611713

  日期：2007.3.1

  Bis-cycloSal-d4T-monophosphates have been synthesized as potentially anti-HIV active "dimeric" prodrugs of 2',3'-dideoxy-2',3'-didehydrothymidine monophosphate (d4TMP). These pronucleotides display a mask-drug ratio of 1:2, a novelty in the field of pronucleotides. Both bis-cycloSal-d4TMP 6 and bis-5-methyl-cycloSal-d4TMP 7 showed increased hydrolytic stability as compared to their "monomeric" counterparts and a completely selective hydrolytic release of d4TMP. The hydrolysis pathway was investigated via P-31 NMR spectroscopy. Moreover, due to the steric bulkiness, compound 6 already displayed strongly reduced inhibitor potency toward human butyrylcholinesterase (BChE), while compound 7 turned out to be devoid of any inhibitory activity against BChE. Partial separation of the diastereomeric mixture of 6 revealed strong dependence of the pronucleotides' properties on the stereochemistry at the phosphorus centers. Both 6and 7 showed good activity against HIV-1 and HIV-2 in wild-type CEM cells in vitro. These compounds were significantly more potent than the parent nucleoside d4T 1in HIV-2-infected TK-deficient CEM cells, indicating an efficient TK-bypass.
• NOVEL <i>CYCLOSAL</i> NUCLEOTIDES WITH REDUCED INHIBITORY POTENCY TOWARD HUMAN BUTYRYLCHOLINESTERASE
  作者：C. Ducho、S. Jessel、N. Gisch、J. Balzarini、C. Meier

  DOI：10.1081/ncn-200061791

  日期：2005.4.1

  Two novel cycloSal-d4T monophosphates (d4TMPs) with increased steric demand have been synthesized via a new synthetic route. While 3-cyclohexyl-cycloSal d4TMP did not show a significantly reduced inhibitory potency toward human butrylylcholinesterase, the opposite was the case for the second novel pronucleotide, bi-(cycloSal-d4TMP).