(S)-1-(2-(4-isobutylphenyl)propanoyl)pyrrolidine-2-carboxylic acid | 919803-16-0

• 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: (S)-1-(2-(4-isobutylphenyl)propanoyl)pyrrolidine-2-carboxylic acid
• 英文别名: 1-[2-(4-isobutylphenyl)-1-oxo-1-propyl]proline；1-(2-(4-isobutylphenyl)propanoyl)pyrrolidine-2-carboxylic acid；1-{2-[4-(2-Methylpropyl)phenyl]propanoyl}-L-proline；(2S)-1-[2-[4-(2-methylpropyl)phenyl]propanoyl]pyrrolidine-2-carboxylic acid
• CAS: 919803-16-0
• 化学式: C₁₈H₂₅NO₃
• 分子量: 303.401
• InChiKey: ZIULIYAPFWDQFO-VYIIXAMBSA-N

物化性质

• 熔点：
  89-93 °C(Solv: ethyl ether (60-29-7); ligroine (8032-32-4))
• 沸点：
  497.0±45.0 °C(Predicted)
• 密度：
  1.134±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-1-(2-(4-isobutylphenyl)propanoyl)pyrrolidine-2-carboxylic acid 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  NSAIDs do not require the presence of a carboxylic acid to exert their anti-inflammatory effect – why do we keep using it?

  摘要：

  The carboxylic acid group (-COOH) present in classical NSAIDs is partly responsible for the gastric toxicity associated with the administration of these drugs. This concept has been extensively proven using NSAID prodrugs. However, the screening of NSAIDs with no carboxylic acid at all has been neglected. The goal of this work was to determine if new NSAID derivatives devoid of acidic moieties would retain the anti-inflammatory activity of the parent compound, without causing gastric toxicity. To test this concept, we replaced the carboxylic acid group in ibuprofen, flurbiprofen, and naproxen with three ammonium moieties. We tested the resulting water-soluble NSAID derivatives for anti-inflammatory and ulcerogenic activity in vitro and in vivo. In this regard, we observed that all non-acidic NSAIDs exerted a potent antiinflammatory activity, suggesting that the acid group in commercial 2-phenylpropionic acid NSAIDs not be an essential requirement for anti-inflammatory activity. These data provide complementary evidence supporting the discontinuation of ulcerogenic acidic NSAIDs.

  DOI：

  10.3109/14756366.2015.1088840
• 作为产物：
  描述：

  布洛芬 在 sodium hydroxide 、 草酰氯 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 (S)-1-(2-(4-isobutylphenyl)propanoyl)pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Design and study of some novel ibuprofen derivatives with potential nootropic and neuroprotective properties

  摘要：

  Six novel ibuprofen derivatives and related structures, incorporating a proline moiety and designed for neurodegenerative disorders, are studied. They possess anti-inflammatory properties and three of them inhibited lipoxygenase. One compound was found to inhibit cyclooxygenase (COX)-2 production in spleenocytes from arthritic rats. The HS-containing compounds are potent antioxidants and one of them protected against glutathione loss after cerebral ischemia/reperfusion. They demonstrated lipid-lowering ability and seem to acquire low gastrointestinal toxicity. Acetylcholinesterase inhibitory activity, found in two of these compounds, may be an asset to their actions. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.056

文献信息

• Enhancement of the Anti-Inflammatory Activity of NSAIDs by Their Conjugation with 3,4,5-Trimethoxybenzyl Alcohol
  作者：Paraskevi Tziona、Panagiotis Theodosis-Nobelos、Georgios Papagiouvannis、Anthi Petrou、Chryssoula Drouza、Eleni A. Rekka

  DOI：10.3390/molecules27072104

  日期：——

  The synthesis of derivatives of three nonspecific COX-1 and COX-2 inhibitors, ibuprofen, ketoprofen, naproxen is presented. These acids were connected via an amide bond with an amino acid (L-proline, L-tyrosine, and beta-alanine) used as a linker. The amino acid carboxylic group was esterified with 3,4,5 trimethoxybenzyl alcohol. The activity of the novel derivatives was examined in vivo on carrageenan-induced

  介绍了三种非特异性 COX-1 和 COX-2 抑制剂布洛芬、酮洛芬、萘普生的衍生物的合成。这些酸通过酰胺键与用作接头的氨基酸（L-脯氨酸、L-酪氨酸和β-丙氨酸）连接。氨基酸羧基用 3,4,5 三甲氧基苄醇酯化。在体内检测了新衍生物对角叉菜胶诱导的炎症的活性，并在体外检测了作为环氧合酶和脂氧合酶抑制剂的活性。发现新化合物比母体药物更有效的抗炎剂。因此，布洛芬 ( 21 ) 和酮洛芬 ( 16) 衍生物减少了 67% 和 91% 的大鼠爪水肿（相关 NSAID 的减少分别为 36% 和 47%）。与起始药物相比，它们对 COX-2 的抑制作用更大（21种抑制67％，布洛芬 46％，19种抑制94％，酮洛芬 49％）。化合物与 COX-1 和 COX-2 活性位点的对接反映了它们的体外活性。因此，19采用了对 COX-1 抑制不利的方向，但它在 COX-2 的结合口袋中有效结合，这与 COX-1
• NSAIDs do not require the presence of a carboxylic acid to exert their anti-inflammatory effect – why do we keep using it?
  作者：Nasir Ullah、Zhangjian Huang、Forough Sanaee、Alexandra Rodriguez-Dimitrescu、Fahad Aldawsari、Fakhreddin Jamali、Atul Bhardwaj、Nazar Ul Islam、Carlos A. Velázquez-Martínez

  DOI：10.3109/14756366.2015.1088840

  日期：2016.11.1

  The carboxylic acid group (-COOH) present in classical NSAIDs is partly responsible for the gastric toxicity associated with the administration of these drugs. This concept has been extensively proven using NSAID prodrugs. However, the screening of NSAIDs with no carboxylic acid at all has been neglected. The goal of this work was to determine if new NSAID derivatives devoid of acidic moieties would retain the anti-inflammatory activity of the parent compound, without causing gastric toxicity. To test this concept, we replaced the carboxylic acid group in ibuprofen, flurbiprofen, and naproxen with three ammonium moieties. We tested the resulting water-soluble NSAID derivatives for anti-inflammatory and ulcerogenic activity in vitro and in vivo. In this regard, we observed that all non-acidic NSAIDs exerted a potent antiinflammatory activity, suggesting that the acid group in commercial 2-phenylpropionic acid NSAIDs not be an essential requirement for anti-inflammatory activity. These data provide complementary evidence supporting the discontinuation of ulcerogenic acidic NSAIDs.
• Design and study of some novel ibuprofen derivatives with potential nootropic and neuroprotective properties
  作者：Ioanna C. Siskou、Eleni A. Rekka、Angeliki P. Kourounakis、Michael C. Chrysselis、Kariofyllis Tsiakitzis、Panos N. Kourounakis

  DOI：10.1016/j.bmc.2006.10.056

  日期：2007.1

  Six novel ibuprofen derivatives and related structures, incorporating a proline moiety and designed for neurodegenerative disorders, are studied. They possess anti-inflammatory properties and three of them inhibited lipoxygenase. One compound was found to inhibit cyclooxygenase (COX)-2 production in spleenocytes from arthritic rats. The HS-containing compounds are potent antioxidants and one of them protected against glutathione loss after cerebral ischemia/reperfusion. They demonstrated lipid-lowering ability and seem to acquire low gastrointestinal toxicity. Acetylcholinesterase inhibitory activity, found in two of these compounds, may be an asset to their actions. (c) 2006 Elsevier Ltd. All rights reserved.