trans-4-[(3H,3aH,6aH)-3-(4-methoxyphenyl)-4,6-dioxo-p-tolyldihydro-2H-pyrrolo[3,4-d]isoxazol-5(3H,6H,6aH)-yl]benzoic acid

• 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-4-[(3H,3aH,6aH)-3-(4-methoxyphenyl)-4,6-dioxo-p-tolyldihydro-2H-pyrrolo[3,4-d]isoxazol-5(3H,6H,6aH)-yl]benzoic acid
• 英文别名: 4-[(3R,3aS,6aR)-3-(4-methoxyphenyl)-2-(4-methylphenyl)-4,6-dioxo-3a,6a-dihydro-3H-pyrrolo[3,4-d][1,2]oxazol-5-yl]benzoic acid
• 化学式: C₂₆H₂₂N₂O₆
• 分子量: 458.47
• InChiKey: AZMMBQCCOVAAAZ-RJGXRXQPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  96.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(3-carboxyacryloylamino)benzoic acid 在 sodium acetate 、 乙酸酐 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 1.5h， 生成 trans-4-[(3H,3aH,6aH)-3-(4-methoxyphenyl)-4,6-dioxo-p-tolyldihydro-2H-pyrrolo[3,4-d]isoxazol-5(3H,6H,6aH)-yl]benzoic acid 、 cis-4-[(3H,3aH,6aH)-3-(4-methoxyphenyl)-4,6-dioxo-p-tolyldihydro-2H-pyrrolo[3,4-d]isoxazol-5(3H,6H,6aH)-yl]benzoic acid
  参考文献：
  名称：

  Synthesis and evaluation of novel 4-[(3H,3aH,6aH)-3-phenyl)-4,6-dioxo-2-phenyldihydro-2H-pyrrolo[3,4-d]isoxazol-5(3H,6H,6aH)-yl]benzoic acid derivatives as potent acetylcholinesterase inhibitors and anti-amnestic agents

  摘要：

  The present study was designed to synthesize and evaluate pyrrolo-isoxazole benzoic acid derivatives as potential acetylcholinesterase (AChE) inhibitors for the management of Alzheimer's disease. The synthesis of pyrrolo-isoxazole benzoic acid derivatives involved ring opening cyclization of p-aminobenzoic acid with maleic anhydride to yield maleanilic acid, which in turn afforded N-arylmaleimide via ring closed cyclization. Azomethine-N-oxides were obtained by condensation of N-arylhydroxylamine with differently substituted benzaldehydes followed by refluxing of N-arylmaleimide with differently substituted azomethine-N-oxides to pyrrolo-isoxazole benzoic acid derivatives as cis- and trans-stereoisomers. The synthesized compounds were evaluated in vitro for AChE inhibitory activity in rat brain homogenate with donepezil as standard AChE inhibitor. Thereafter, the most potent test compound was evaluated for in vitro butyrylcholinesterase inhibitory activity and in vivo memory evaluation in scopolamine (0.4 mg/kg)-induced amnesia in mice by employing Morris water maze test. All pyrrolo-isoxazole benzoic acid derivatives demonstrated potent AChE inhibitory activity. Most of compounds exhibited similar activity to donepezil and four of them (7h, 7i, 8i, and 8h, IC50 = 19.1 +/- 3 1.9-17.5 +/- 1.5 nM) displayed higher inhibitory activity as compared to donepezil (21.5 +/- 3.2 nM) with compound 8ia (IC50 = 17.5 +/- 1.5 nM) being the most active one. The test compound 8ia also ameliorated scopolamine-induced amnesia in mice in terms of restoration of time spent in target quadrant (TSTQ) and escape latency time (ELT). It may be concluded that pyrrolo-isoxazole benzoic acid derivatives may be employed as potential AChE inhibitors. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2011.05.027