methyl 1-[4-(1-methoxy-1-oxopropan-2-yl)-3-nitrobenzyl]-2-oxocyclopentanecarboxylate | 1313592-01-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 1-[4-(1-methoxy-1-oxopropan-2-yl)-3-nitrobenzyl]-2-oxocyclopentanecarboxylate
• CAS: 1313592-01-6
• 化学式: C₁₈H₂₁NO₇
• 分子量: 363.367
• InChiKey: PXTVEKUDKDVNTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.33
• 重原子数：
  26.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  112.81
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl 1-[4-(1-methoxy-1-oxopropan-2-yl)-3-nitrobenzyl]-2-oxocyclopentanecarboxylate 在 盐酸 、 sodium hydroxide 作用下， 以 水 、 乙醇 为溶剂， 以69.4%的产率得到sodium 2-{2-nitro-4-[(2-oxocyclopentyl)methyl]phenyl}propanoate
  参考文献：
  名称：

  Synthesis and biological evaluation of loxoprofen derivatives

  摘要：

  Non-steroidal anti-inflammatory drugs (NSAIDs) achieve their anti-inflammatory actions through an inhibitory effect on cyclooxygenase (COX). Two COX subtypes, COX-1 and COX-2, are responsible for the majority of COX activity at the gastrointestinal mucosa and in tissues with inflammation, respectively. We previously suggested that both gastric mucosal cell death due to the membrane permeabilization activity of NSAIDs and COX-inhibition at the gastric mucosa are involved in NSAID-induced gastric lesions. We have also reported that loxoprofen has the lowest membrane permeabilization activity among the NSAIDs we tested. In this study, we synthesized a series of loxoprofen derivatives and examined their membrane permeabilization activities and inhibitory effects on COX-1 and COX-2. Among these derivatives, 2-{4'-hydroxy-5-[(2-oxocyclopentyl)methyl]biphenyl-2-yl}propanoate 31 has a specificity for COX-2 over COX-1. Compared to loxoprofen, oral administration of 31 to rats produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that 31 is likely to be a therapeutically beneficial and safer NSAID. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.050
• 作为产物：
  描述：

  4-甲基-2-硝基苯乙酸 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 sodium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 四氯化碳 、 水 、 丙酮 为溶剂， 生成 methyl 1-[4-(1-methoxy-1-oxopropan-2-yl)-3-nitrobenzyl]-2-oxocyclopentanecarboxylate
  参考文献：
  名称：

  Synthesis and biological evaluation of loxoprofen derivatives

  摘要：

  Non-steroidal anti-inflammatory drugs (NSAIDs) achieve their anti-inflammatory actions through an inhibitory effect on cyclooxygenase (COX). Two COX subtypes, COX-1 and COX-2, are responsible for the majority of COX activity at the gastrointestinal mucosa and in tissues with inflammation, respectively. We previously suggested that both gastric mucosal cell death due to the membrane permeabilization activity of NSAIDs and COX-inhibition at the gastric mucosa are involved in NSAID-induced gastric lesions. We have also reported that loxoprofen has the lowest membrane permeabilization activity among the NSAIDs we tested. In this study, we synthesized a series of loxoprofen derivatives and examined their membrane permeabilization activities and inhibitory effects on COX-1 and COX-2. Among these derivatives, 2-{4'-hydroxy-5-[(2-oxocyclopentyl)methyl]biphenyl-2-yl}propanoate 31 has a specificity for COX-2 over COX-1. Compared to loxoprofen, oral administration of 31 to rats produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that 31 is likely to be a therapeutically beneficial and safer NSAID. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.050