4-(4-Methoxymethoxy-phenyl)-butyric acid methoxymethyl ester | 184592-40-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(4-Methoxymethoxy-phenyl)-butyric acid methoxymethyl ester
• 英文别名: Methoxymethyl 4-[4-(methoxymethoxy)phenyl]butanoate
• CAS: 184592-40-3
• 化学式: C₁₄H₂₀O₅
• 分子量: 268.31
• InChiKey: VSZZXGUNTLGIDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-Methoxymethoxy-phenyl)-butyric acid methoxymethyl ester 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 3,5-Bis-benzyloxy-4-(2-benzyloxy-6-benzyloxycarbonyl-benzoyl)-benzoic acid 4-(4-methoxymethoxy-phenyl)-butyl ester
  参考文献：
  名称：

  Synthesis and Protein Kinase C Inhibitory Activities of Acyclic Balanol Analogs That Are Highly Selective for Protein Kinase C over Protein Kinase A

  摘要：

  A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta(I), beta(II), gamma, delta, epsilon, and eta PKC: isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.

  DOI：

  10.1021/jm960581w
• 作为产物：
  描述：

  4-(4-甲氧基苯基)丁酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 N,N-二异丙基乙胺 、 乙硫醇钠 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 103.0h， 生成 4-(4-Methoxymethoxy-phenyl)-butyric acid methoxymethyl ester
  参考文献：
  名称：

  Synthesis and Protein Kinase C Inhibitory Activities of Acyclic Balanol Analogs That Are Highly Selective for Protein Kinase C over Protein Kinase A

  摘要：

  A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta(I), beta(II), gamma, delta, epsilon, and eta PKC: isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.

  DOI：

  10.1021/jm960581w

文献信息

• Synthesis and Protein Kinase C Inhibitory Activities of Acyclic Balanol Analogs That Are Highly Selective for Protein Kinase C over Protein Kinase A
  作者：Jean M. Defauw、Marcia M. Murphy、G. Erik Jagdmann、Hong Hu、John W. Lampe、Sean P. Hollinshead、Thomas J. Mitchell、Heidi M. Crane、Julia M. Heerding、José S. Mendoza、Jefferson E. Davis、James W. Darges、Frederick R. Hubbard、Steven E. Hall

  DOI：10.1021/jm960581w

  日期：1996.1.1

  A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta(I), beta(II), gamma, delta, epsilon, and eta PKC: isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.