4-[(diethoxyphosphoryl)-methyl]benzoyl chloride | 118578-91-9

• 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-[(diethoxyphosphoryl)-methyl]benzoyl chloride
• 英文别名: 4-<(diethoxyphosphinyl)methyl>benzoic acid chloride；4-<(diethoxyphosphoryl)methyl>benzoyl chloride；diethyl 4-(chlorocarbonyl)benzylphosphonate；4-diethylphosphonomethyl benzoyl chloride；4-diethoxyphosphinoylmethylbenzoyl chloride；4-[(diethoxyphosphoryl)methyl]benzoyl chloride；4-(diethoxyphosphorylmethyl)benzoyl chloride
• CAS: 118578-91-9
• 化学式: C₁₂H₁₆ClO₄P
• 分子量: 290.683
• InChiKey: HQXNAOPPIPWBRE-UHFFFAOYSA-N

物化性质

• 沸点：
  399.3±35.0 °C(Predicted)
• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[(diethoxyphosphoryl)-methyl]benzoyl chloride 在 甲醇 、 4-二甲氨基吡啶 、 三甲基溴硅烷 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.0h， 生成 4-(2-(benzylthio)-7-(2-(4-chlorophenoxy)ethyl)-6-oxo-6,7-dihydro-1Hpurin-8-yl)benzylphosphonic acid
  参考文献：
  名称：

  Structure-Guided Design, Synthesis, and Evaluation of Guanine-Derived Inhibitors of the eIF4E mRNA–Cap Interaction

  摘要：

  The eukaryotic initiation factor 4E (eIF4E) plays a central role in the initiation of gene translation and subsequent protein synthesis by binding the 5' terminal mRNA cap structure. We designed and synthesized a series of novel compounds that display potent binding affinity against eIF4E despite their lack of a ribose moiety, phosphate, and positive charge as present in m7-GMP. The biochemical activity of compound 33 is 95 nM for eIF4E in an SPA binding assay. More importantly, the compound has an IC50 of 2.5 mu M for inhibiting cap-dependent mRNA translation in a rabbit reticular cell extract assay (RRL-IVT). This series of potent, truncated analogues could serve as a promising new starting point toward the design of neutral eIF4E inhibitors with physicochemical properties suitable for cellular activity assessment.

  DOI：

  10.1021/jm300037x
• 作为产物：
  描述：

  对溴甲基苯甲酸 在 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 3.0h， 生成 4-[(diethoxyphosphoryl)-methyl]benzoyl chloride
  参考文献：
  名称：

  Structure-Guided Design, Synthesis, and Evaluation of Guanine-Derived Inhibitors of the eIF4E mRNA–Cap Interaction

  摘要：

  The eukaryotic initiation factor 4E (eIF4E) plays a central role in the initiation of gene translation and subsequent protein synthesis by binding the 5' terminal mRNA cap structure. We designed and synthesized a series of novel compounds that display potent binding affinity against eIF4E despite their lack of a ribose moiety, phosphate, and positive charge as present in m7-GMP. The biochemical activity of compound 33 is 95 nM for eIF4E in an SPA binding assay. More importantly, the compound has an IC50 of 2.5 mu M for inhibiting cap-dependent mRNA translation in a rabbit reticular cell extract assay (RRL-IVT). This series of potent, truncated analogues could serve as a promising new starting point toward the design of neutral eIF4E inhibitors with physicochemical properties suitable for cellular activity assessment.

  DOI：

  10.1021/jm300037x

文献信息

• Phosphonic diester derivatives
  申请人：Otsuka Pharmaceutical Factory, Inc.

  公开号：US05624918A1

  公开（公告）日：1997-04-29

  The present invention provides a phosphonic diester derivative of the following general formula (1): ##STR1## wherein A represents an oxygen atom or a sulfur atom; R.sup.1, R.sup.2, R.sup.9 and R.sup.10 are the same or different and they each represent a hydrogen atom, a lower alkoxy group, a nitro group, a lower alkyl group, a halogen-substituted lower alkyl group or a halogen atom; R.sup.3 represents a phenyl group, --B--R.sup.6 (wherein B represents an oxygen atom or a sulfur atom and R.sup.6 represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, a phenyl group, a phenyl(lower)alkyl group optionally having a halogen atom as a substituent on the phenyl ring, a phenoxy(lower)alkyl group, a lower alkoxycarbonyl(lower)alkyl group, a carboxy(lower)alkyl group or a lower alkenyl group) or --NR.sup.7 R.sup.8 (wherein R.sup.7 and R.sup.8 and are the same or different and they each represent a hydrogen atom, a lower alkyl group, an amino group or a cycloalkyl group or combinedly represent a lower alkylene group); and R.sup.4 and R.sup.5 are the same or different and they each represent a hydrogen atom or a lower alkyl group. The derivative of the present invention is useful as therapeutic agents for hyperlipidemic diseases, hypertension, diabetes and the like.

  本发明提供了以下一般式（1）的膦酸二酯衍生物：其中A代表氧原子或硫原子；R.sup.1、R.sup.2、R.sup.9和R.sup.10相同或不同，分别代表氢原子、较低的烷氧基、硝基、较低烷基、卤素取代的较低烷基或卤素原子；R.sup.3代表苯基、--B--R.sup.6（其中B代表氧原子或硫原子，R.sup.6代表氢原子、较低烷基、环烷基、苯基、苯（较低）烷基，在苯环上可能有卤素原子取代，苯氧基（较低）烷基、较低烷氧羰基（较低）烷基、羧基（较低）烷基或较低烯基）或--NR.sup.7 R.sup.8（其中R.sup.7和R.sup.8相同或不同，分别代表氢原子、较低烷基、氨基、环烷基或组合地代表较低烷基烯基）；R.sup.4和R.sup.5相同或不同，分别代表氢原子或较低烷基。本发明的衍生物可用作治疗高脂血症、高血压、糖尿病等疾病的治疗药物。
• Synthesis and Hypolipidemic Activities of Novel 2-[4-[(Diethoxyphosphoryl)methyl]phenyl]quinazolines and 4(3<i>H</i>)-Quinazolinones
  作者：Yasuhisa Kurogi、Yasuhide Inoue、Kazuhiko Tsutsumi、Shizuo Nakamura、Kazushi Nagao、Hiroki Yoshitsugu、Yoshihiko Tsuda

  DOI：10.1021/jm9506938

  日期：1996.1.1

  Derivatives bearing a 4-[(diethoxyphosphoryl)-methyl]phenyl] group at the 2-position were found to lower triglyceride and total cholesterol levels. In accord with the decrease in log P*, quinazolines and 4(3H)-quinazolinones showed good absorption and hypolipidemic activity. When the quinazolinone ring system is substituted at positions 6 and 7 with methoxy groups, increased hypolipidemic activity was observed

  新型化合物NO-1886，4-[（（二乙氧基磷酰基）甲基] -N-（4-溴-2-氰基苯基）-苯甲酰胺，是一种降血脂药，似乎增加了大鼠脂蛋白脂肪酶的活性。合成了NO-1886的各种类似物，以研究这种降血脂药的构效关系。通过环化NO-1886衍生物制备了一系列新的喹唑啉和4（3H）-喹唑啉酮。发现在2-位带有4-[（（二乙氧基磷酰基）-甲基]苯基]基团的衍生物降低甘油三酸酯和总胆固醇水平。与log P *的降低一致，喹唑啉和4（3H）-喹唑啉酮显示出良好的吸收和降血脂活性。当喹唑啉酮环系统在6和7位被甲氧基取代时，观察到降血脂活性增加。
• Composition for preventing and treating cataract
  申请人：Otsuka Pharmaceutical Factory, Inc.

  公开号：US05618801A1

  公开（公告）日：1997-04-08

  The present invention provides an agent for preventing and treating cataract comprising, as an active ingredient, a carboxylic acid amide derivative represented by the general formula: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and X are as defined above. The present invention has a marked preventive and therapeutic effect on the cataract belonging to various classifications and particularly on the diabetic cataract.

  本发明提供了一种预防和治疗白内障的药剂，其包括一种由一般式表示的羧酸酰胺衍生物作为活性成分： ##STR1## 其中R1、R2、R3、R4和X如上所定义。本发明对于属于不同分类的白内障，特别是糖尿病性白内障具有明显的预防和治疗效果。
• Synthesis and Biological Activity of the Metabolites of Diethyl 4-((4-Bromo-2-cyanophenyl)carbamoyl)benzylphosphonate (NO-1886).
  作者：Kiyoto GOTO、Shizuo NAKAMURA、Yujiro MORIOKA、Mitsuyoshi KONDO、Shinsaku NAITO、Kazuhiko TSUTSUMI

  DOI：10.1248/cpb.44.547

  日期：——

  Five metabolites of diethyl 4-[(4-bromo-2-cyanophenyl)carbamoyl]benzylphosphonate (NO-1886) (1) were synthesized to confirm their proposed structures. The metabolites (2-6) were found to be identical with the synthesized compounds. These metabolites were orally administered to Triton WR-1339-induced hypertriglyceridemic rats, and the plasma levels of triglycerides were measured to estimate lipoprotein

  合成了4-[（4-溴-2-氰基苯基）氨基甲酰基]苄基膦酸二乙酯（NO-1886）（1）的五种代谢物，以证实它们的结构。发现代谢物（2-6）与合成的化合物相同。将这些代谢物口服给予Triton WR-1339诱导的高甘油三酸酯血症大鼠，并测量血浆甘油三酸酯水平以估计脂蛋白脂酶活性。所有的代谢物均显示出比NO-1886更低的效力。
• Carboxamide compounds, processes for preparing the same and a
  申请人：Otsuka Pharmaceutical Factory, Inc.

  公开号：US04971957A1

  公开（公告）日：1990-11-20

  Novel carboxamide compounds represented by the general formula (I) possess excellent activities for lowering lipids and thus they are useful as agents for treating and preventing various diseases (hyperlipidemia) such as hypercholesterolemia, hypertriglyceridemia, hyperphospholipidemia, hyperlipacidemia, and the like.

  一般式为（I）的新型羧酰胺化合物具有降低脂质的优良活性，因此它们可用作治疗和预防各种疾病（高脂血症），如高胆固醇血症，高甘油三酯血症，高磷脂血症，高脂酸血症等的药物。