3-Benzyloxy-2-(2,6-bis-benzyloxy-4-chlorocarbonyl-benzoyl)-benzoic acid benzyl ester | 167832-93-1

• 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-Benzyloxy-2-(2,6-bis-benzyloxy-4-chlorocarbonyl-benzoyl)-benzoic acid benzyl ester
• 英文别名: Benzyl 2-[4-carbonochloridoyl-2,6-bis(phenylmethoxy)benzoyl]-3-phenylmethoxybenzoate
• CAS: 167832-93-1
• 化学式: C₄₃H₃₃ClO₇
• 分子量: 697.184
• InChiKey: RGKUTBWMZVAPBV-UHFFFAOYSA-N

物化性质

• 沸点：
  842.4±65.0 °C(Predicted)
• 密度：
  1.275±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  51
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-Benzyloxy-2-(2,6-bis-benzyloxy-4-chlorocarbonyl-benzoyl)-benzoic acid benzyl ester 在 palladium dihydroxide 4-二甲氨基吡啶 、 氢气 、 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 (R)-2-({2,6-dihydroxy-4-[({3-(4-hydroxyphenyl)-2-[(phenylsulfonyl)amino]propyl}oxy)carbonyl]phenyl}carbonyl)-3-hydroxybenzoic acid
  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 The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group.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-(6-Benzyloxy-2-(benzyloxycarbonyl)benzoyl)-3,5-dibenzyloxybenzoic Acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 3-Benzyloxy-2-(2,6-bis-benzyloxy-4-chlorocarbonyl-benzoyl)-benzoic acid benzyl ester
  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

• Total Synthesis of (-)-Balanol
  作者：John W. Lampe、Philip F. Hughes、Christopher K. Biggers、Shelley H. Smith、Hong Hu

  DOI：10.1021/jo00097a014

  日期：1994.9

  (-)-Balanol, a fungal metabolite with potent protein kinase C inhibitory properties, has been prepared in a total synthesis which makes use of an anionic homo-Fries rearrangement approach to the benzophenone subunit and in which the azepane subunit is obtained from (2S,3R)-3-hydroxylysine.

  (-)-Balanol是一种具有强效蛋白激酶C抑制活性的真菌 metabolite，我们已通过全合成方法成功制备。该合成方法采用了阴离子同系Fries重排策略来构建苯丙酮（benzophenone）部分，同时将叠氮（azepane）部分由(2S,3R)-3-羟基赖氨酸（3-hydroxylysine）获取。
• Potent and selective PKC inhibitory 5-membered ring analogs of balanol with replacement of the carboxamide moiety
  作者：G.Erik Jagdmann、Jean M. Defauw、John W. Lampe、James W. Darges、Kiyomi Kalter

  DOI：10.1016/0960-894x(96)00311-3

  日期：1996.8

  Balanol ((-)-1) is a potent protein kinase inhibitory natural product isolated from the fungus Verticillium balanoides. The lack of cellular activity and protein kinase C selectivity in balanol has prompted a search for analogs that incorporate these properties, This paper describes the synthesis and biological activity of such compounds with substitution similar to balanol, but with a single atom bridge in place of the carboxamide moiety. Copyright (C) 1996 Elsevier Science Ltd
• Synthesis and protein kinase C inhibitory activities of indane analogs of balanol
  作者：Hong Hu、Sean P. Hollinshead、Steven E. Hall、Kiyomi Kalter、Lawrence M. Ballas

  DOI：10.1016/0960-894x(96)00151-5

  日期：1996.4
• 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.