3,5-Bis-benzyloxy-4-(2-benzyloxy-naphthalene-1-carbonyl)-benzoic acid | 167832-87-3

• 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: 3,5-Bis-benzyloxy-4-(2-benzyloxy-naphthalene-1-carbonyl)-benzoic acid
• 英文别名: 3,5-Bis(phenylmethoxy)-4-(2-phenylmethoxynaphthalene-1-carbonyl)benzoic acid
• CAS: 167832-87-3
• 化学式: C₃₉H₃₀O₆
• 分子量: 594.664
• InChiKey: JJVXVHXQFRHUFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,5-Bis-benzyloxy-4-(2-benzyloxy-naphthalene-1-carbonyl)-benzoic acid 在 4-二甲氨基吡啶 、 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 (3R,4R)-3-(4-Benzyloxy-benzoylamino)-4-[3,5-bis-benzyloxy-4-(2-benzyloxy-naphthalene-1-carbonyl)-benzoyloxy]-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Protein Kinase Inhibitory Activity of Balanol Analogues with Modified Benzophenone Subunits

  摘要：

  A series of analogues of the protein kinase C (PKC) inhibitory natural product balanol which bear modified benzophenone subunits are described. The analogues were designed with the goal of uncovering structure - activity features that could be used in the development of PKC inhibitors with a reduced polar character compared to balanol itself. The results of these studies suggest that most of the benzophenone features found in the natural product are important for obtaining potent PKC inhibitory compounds. However, several modifications were found to lead to selective inhibitors of the related enzyme protein kinase A (PKA), and several specific modifications to the polar structural elements of the benzophenone were found to provide potent PKC inhibitors. In particular, it was found that replacement of the benzophenone carboxylate with bioisosteric equivalents could lead to potent analogues. Further, a tolerance for lipophilic substituents on the terminal benzophenone ring was uncovered. These results are discussed in light of recently available structural information for PKA.

  DOI：

  10.1021/jm020018f
• 作为产物：
  描述：

  2-苄氧基-1-萘醛 在 chromium(VI) oxide 、 正丁基锂 、 甲酸 、 硫酸 作用下， 以 四氢呋喃 、 环己烷 、 丙酮 为溶剂， 反应 4.16h， 生成 3,5-Bis-benzyloxy-4-(2-benzyloxy-naphthalene-1-carbonyl)-benzoic acid
  参考文献：
  名称：

  Synthesis and Protein Kinase Inhibitory Activity of Balanol Analogues with Modified Benzophenone Subunits

  摘要：

  A series of analogues of the protein kinase C (PKC) inhibitory natural product balanol which bear modified benzophenone subunits are described. The analogues were designed with the goal of uncovering structure - activity features that could be used in the development of PKC inhibitors with a reduced polar character compared to balanol itself. The results of these studies suggest that most of the benzophenone features found in the natural product are important for obtaining potent PKC inhibitory compounds. However, several modifications were found to lead to selective inhibitors of the related enzyme protein kinase A (PKA), and several specific modifications to the polar structural elements of the benzophenone were found to provide potent PKC inhibitors. In particular, it was found that replacement of the benzophenone carboxylate with bioisosteric equivalents could lead to potent analogues. Further, a tolerance for lipophilic substituents on the terminal benzophenone ring was uncovered. These results are discussed in light of recently available structural information for PKA.

  DOI：

  10.1021/jm020018f

文献信息

• BALANOIDS
  申请人：SPHINX PHARMACEUTICALS CORPORATION

  公开号：EP0687249A1

  公开（公告）日：1995-12-20
• [EN] BALANOIDS<br/>[FR] BALANOIDES
  申请人：——

  公开号：WO1994020062A2

  公开（公告）日：1994-09-15

  [EN] A novel class of therapeutic compounds, denominated Balanoids, is disclosed. Balanoids have protein kinase C inhibitory activity and selectivity among the isoforms of protein kinase C. Balanoids are useful for treatment of diseases related to protein kinase C in animals, especially humans and is especially indicated for treatment of inflammatory diseases.
  [FR] Nouvelle classe de composés thérapeutiques nommés balanoïdes. Lesdits composés possèdent une activité inhibitrice de la protéine kinase C et une sélectivité parmi les isoformes de la protéine kinase C. Les balanoïdes sont utiles pour traiter les maladies liées à la protéine kinase C chez les animaux, en particulier chez leshumains, et ils sont particulièrement indiqués pour traiter les maladies inflammatoires.
• Synthesis and Protein Kinase Inhibitory Activity of Balanol Analogues with Modified Benzophenone Subunits
  作者：John W. Lampe、Christopher K. Biggers、Jean M. Defauw、Robert J. Foglesong、Steven E. Hall、Julia M. Heerding、Sean P. Hollinshead、Hong Hu、Philip F. Hughes、G. Erik Jagdmann、Mary George Johnson、Yen-Shi Lai、Christopher T. Lowden、Michael P. Lynch、José S. Mendoza、Marcia M. Murphy、Joseph W. Wilson、Lawrence M. Ballas、Kiyomi Carter、James W. Darges、Jefferson E. Davis、Frederick R. Hubbard、Mark L. Stamper

  DOI：10.1021/jm020018f

  日期：2002.6.1

  A series of analogues of the protein kinase C (PKC) inhibitory natural product balanol which bear modified benzophenone subunits are described. The analogues were designed with the goal of uncovering structure - activity features that could be used in the development of PKC inhibitors with a reduced polar character compared to balanol itself. The results of these studies suggest that most of the benzophenone features found in the natural product are important for obtaining potent PKC inhibitory compounds. However, several modifications were found to lead to selective inhibitors of the related enzyme protein kinase A (PKA), and several specific modifications to the polar structural elements of the benzophenone were found to provide potent PKC inhibitors. In particular, it was found that replacement of the benzophenone carboxylate with bioisosteric equivalents could lead to potent analogues. Further, a tolerance for lipophilic substituents on the terminal benzophenone ring was uncovered. These results are discussed in light of recently available structural information for PKA.