trans-3-(4-methylbenzamido)-4-[4-(2-carboxy-6-hydroxybenzoyl)-3,5-dihydroxybenzoyloxy]perhydroazepine trifluoroacetate

• 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: trans-3-(4-methylbenzamido)-4-[4-(2-carboxy-6-hydroxybenzoyl)-3,5-dihydroxybenzoyloxy]perhydroazepine trifluoroacetate
• 化学式: 5C₂HF₃O₂*4C₂₉H₂₈N₂O₉
• 分子量: 2764.32
• InChiKey: FRPFTSOAXDLYHO-AQHBPOCSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  47.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  219.79
• 氢给体数：
  7.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  4-(6-Benzyloxy-2-(benzyloxycarbonyl)benzoyl)-3,5-dibenzyloxybenzoic Acid 在 palladium dihydroxide 4-二甲氨基吡啶 、 草酰氯 、 氢气 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 26.0h， 生成 trans-3-(4-methylbenzamido)-4-[4-(2-carboxy-6-hydroxybenzoyl)-3,5-dihydroxybenzoyloxy]perhydroazepine trifluoroacetate
  参考文献：
  名称：

  Synthesis and protein kinase C inhibitory activities of balanol analogues with modification of 4-hydroxybenzamido moiety

  摘要：

  A series of racemic balanol analogues with modification of the benzamido moiety of balanol have been synthesized and evaluated for their inhibitory activities against human protein kinase C isozymes (PKC-alpha, -beta I, -beta II, -gamma, -delta, -epsilon, and -eta). The structural modification includes replacement of the 4-hydroxyphenyl group with variously substituted phenyl rings, substitution of the amide linkage with a sulfonamide or an ester, and replacement of the 4-hydroxyphenyl substructure with a hydroxyl substituted indole or a hydroxybenzyl group. In general, these analogues were found to be less potent than balanol, but a number of analogues were identified with improved isozyme selectivity. The structure-activity relationship studies of these analogues also indicated that (1) the optimal general PKC inhibition requires a free 4-hydroxyl group in the benzamido portion of the molecule, (2) the amide linkage of the benzamido moiety is important for PKC inhibition, and (3) the conformation associated with the benzamido moiety seems to have a profound effect on PKC inhibition. The requirement of a free 4-hydroxyl group in conjunction with an appropriate conformation of the benzamido moiety for optimal PKC inhibition suggests that the 4-hydroxyphenyl group may be involved in a specific inhibitor-enzyme interaction important for PKC inhibition. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00125-9

文献信息

• Synthesis and protein kinase C inhibitory activities of balanol analogues with modification of 4-hydroxybenzamido moiety
  作者：Hong Hu、Jose S. Mendoza、Christopher T. Lowden、Lawrence M. Ballas、William P. Janzen

  DOI：10.1016/s0968-0896(97)00125-9

  日期：1997.9

  A series of racemic balanol analogues with modification of the benzamido moiety of balanol have been synthesized and evaluated for their inhibitory activities against human protein kinase C isozymes (PKC-alpha, -beta I, -beta II, -gamma, -delta, -epsilon, and -eta). The structural modification includes replacement of the 4-hydroxyphenyl group with variously substituted phenyl rings, substitution of the amide linkage with a sulfonamide or an ester, and replacement of the 4-hydroxyphenyl substructure with a hydroxyl substituted indole or a hydroxybenzyl group. In general, these analogues were found to be less potent than balanol, but a number of analogues were identified with improved isozyme selectivity. The structure-activity relationship studies of these analogues also indicated that (1) the optimal general PKC inhibition requires a free 4-hydroxyl group in the benzamido portion of the molecule, (2) the amide linkage of the benzamido moiety is important for PKC inhibition, and (3) the conformation associated with the benzamido moiety seems to have a profound effect on PKC inhibition. The requirement of a free 4-hydroxyl group in conjunction with an appropriate conformation of the benzamido moiety for optimal PKC inhibition suggests that the 4-hydroxyphenyl group may be involved in a specific inhibitor-enzyme interaction important for PKC inhibition. (C) 1997 Elsevier Science Ltd.