ethyl (2S)-2-[(5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carbonyl)amino]-3-(1H-indol-3-yl)propanoate | 1093407-69-2

• 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: ethyl (2S)-2-[(5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carbonyl)amino]-3-(1H-indol-3-yl)propanoate
• CAS: 1093407-69-2
• 化学式: C₂₈H₂₇N₃O₄
• 分子量: 469.54
• InChiKey: NZENKTVZVZYBPP-YANBTOMASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  93.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  L-色氨酸乙酯盐酸盐 、 酮咯酸 在 N,N'-二环己基碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以70%的产率得到ethyl (2S)-2-[(5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carbonyl)amino]-3-(1H-indol-3-yl)propanoate
  参考文献：
  名称：

  Synthesis, characterization and pharmacological evaluation of amide prodrugs of ketorolac

  摘要：

  Ketorolac (KC) suffers from the general side effects of NSAIDs, owing to presence of free carboxylic acid group. The study aimed to retard the adverse effects of gastrointestinal origin. Ten prodrugs of KC were synthesized by amidation with ethyl esters of amino acids, namely, glycine, L-phenylalanine, L-tryptophan, L-valine, L-isoleucine, L-alanine, L-leucine, L-glutamic acid, L-aspartic acid and P-alanine. Purified synthesized prodrugs were characterized by m.p., TLC, solubility, partition coefficients, elemental analyses, UV, FTIR, NMR and MS. Synthesized prodrugs were subjected for biopharmaceutical studies, analgesic, anti-inflammatory activities and ulcerogenic index. Marked reduction of ulcerogenic index and comparable analgesic, anti-inflammatory activities were obtained in all cases as compared to KC. Among synthesized prodrugs, viz. AR-11, AR-19 and AR-20 showed excellent pharmacological response and encouraging hydrolysis rate both in SIF and in 80% human plasma. Prodrugs with increased aliphatic side chain length or introduction of aromatic substituent showed enhanced partition coefficient but diminished dissolution and hydrolysis rates. Such prodrugs can be considered for sustained release purpose. (C) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.09.011

文献信息

• Synthesis, characterization and pharmacological evaluation of amide prodrugs of ketorolac
  作者：Ashutosh Mishra、Ravichandran Veerasamy、Prateek Kumar Jain、Vinod Kumar Dixit、Ram Kishor Agrawal

  DOI：10.1016/j.ejmech.2007.09.011

  日期：2008.11

  Ketorolac (KC) suffers from the general side effects of NSAIDs, owing to presence of free carboxylic acid group. The study aimed to retard the adverse effects of gastrointestinal origin. Ten prodrugs of KC were synthesized by amidation with ethyl esters of amino acids, namely, glycine, L-phenylalanine, L-tryptophan, L-valine, L-isoleucine, L-alanine, L-leucine, L-glutamic acid, L-aspartic acid and P-alanine. Purified synthesized prodrugs were characterized by m.p., TLC, solubility, partition coefficients, elemental analyses, UV, FTIR, NMR and MS. Synthesized prodrugs were subjected for biopharmaceutical studies, analgesic, anti-inflammatory activities and ulcerogenic index. Marked reduction of ulcerogenic index and comparable analgesic, anti-inflammatory activities were obtained in all cases as compared to KC. Among synthesized prodrugs, viz. AR-11, AR-19 and AR-20 showed excellent pharmacological response and encouraging hydrolysis rate both in SIF and in 80% human plasma. Prodrugs with increased aliphatic side chain length or introduction of aromatic substituent showed enhanced partition coefficient but diminished dissolution and hydrolysis rates. Such prodrugs can be considered for sustained release purpose. (C) 2007 Elsevier Masson SAS. All rights reserved.