1-benzyl-3-[(4-phenylmethoxyphenyl)methylidene]pyrrolidine-2,4-dione | 181472-32-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-benzyl-3-[(4-phenylmethoxyphenyl)methylidene]pyrrolidine-2,4-dione
• CAS: 181472-32-2
• 化学式: C₂₅H₂₁NO₃
• 分子量: 383.447
• InChiKey: YPNIMVDHJGRWBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.26
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-benzyl-3-[(4-phenylmethoxyphenyl)methylidene]pyrrolidine-2,4-dione 在 palladium dihydroxide 、 镍 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 正丁基锂 、 氢气 、 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 25.0~70.0 ℃ 、310.27 kPa 条件下， 反应 46.92h， 生成
  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 The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group.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：

  1-benzyl-4-methoxy-1H-pyrrol-2(5H)-one 在 硫酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 1-benzyl-3-[(4-phenylmethoxyphenyl)methylidene]pyrrolidine-2,4-dione
  参考文献：
  名称：

  Potent and selective PKC inhibitory 5-membered ring analogs of balanol with replacement of the carboxamide moiety

  摘要：

  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

  DOI：

  10.1016/0960-894x(96)00311-3