(S,S)-N-<2-(6-methoxy-2-naphthyl)propionyl>proline | 125182-16-3

• 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,S)-N-<2-(6-methoxy-2-naphthyl)propionyl>proline
• 英文别名: (S,S)-1-(2-(6-methoxynaphthalen-2-yl)propanoyl)pyrrolidine-2-carboxylic acid；1-[2-(6-methoxynaphthalen-2-yl)-1-oxo-1-propyl]proline；1-(2-(6-methoxynaphthalen-2-yl)propanoyl)pyrrolidine-2-carboxylic acid；(2S)-1-[(2S)-2-(6-methoxynaphthalen-2-yl)propanoyl]pyrrolidine-2-carboxylic acid
• CAS: 125182-16-3
• 化学式: C₁₉H₂₁NO₄
• 分子量: 327.38
• InChiKey: VCGDMBCHUGSFIA-SJCJKPOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S,S)-N-<2-(6-methoxy-2-naphthyl)propionyl>proline 在 盐酸 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 、 水 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：

  (S,S)-N-<2-(6-methoxy-2-naphthyl)propionyl>proline t-butyl ester 在 三氟乙酸 作用下， 以 甲苯 为溶剂， 反应 1.5h， 以53.5%的产率得到(S,S)-N-<2-(6-methoxy-2-naphthyl)propionyl>proline
  参考文献：
  名称：

  Sunjic, Vitomir; Habus, Ivan; Comisso, Giovanni, Gazzetta Chimica Italiana, 1989, vol. 119, # 4, p. 229 - 234

  摘要：

  DOI：

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
• Synthesis and pharmacochemical study of novel polyfunctional molecules combining anti-inflammatory, antioxidant, and hypocholesterolemic properties
  作者：Christos M. Doulgkeris、Dimitrios Galanakis、Angeliki P. Kourounakis、Karyofyllis C. Tsiakitzis、Antonios M. Gavalas、Phaedra T. Eleftheriou、Panagiotis Victoratos、Eleni A. Rekka、Panos N. Kourounakis

  DOI：10.1016/j.bmcl.2005.11.027

  日期：2006.2

  We have designed and synthesized a series of novel molecules having a residue of a classical NSAID and an antioxidant moiety, both attached through amide bonds to a known nootropic structure, an L-proline, frans-4-hydroxy-L-proline or DL-pipecolinic acid residue. The compounds were found to retain anti-inflammatory and antioxidant activities, to acquire hypocholesterolemic action, and to possess a greatly reduced gastrointestinal toxicity. The novel molecules could find useful applications, among others, in slowing the progression or delaying the onset of neurodegenerative diseases. (c) 2005 Elsevier Ltd. All rights reserved.
• Compounds against inflammation and oxidative insult as potential agents for neurodegenerative disorders
  作者：Christos M. Doulgkeris、Ioanna C. Siskou、Nikoletta Xanthopoulou、Vassiliki Lagouri、Constantina Kravaritou、Phaedra Eleftheriou、Panos N. Kourounakis、Eleni A. Rekka

  DOI：10.1007/s00044-011-9726-x

  日期：2012.9

  Amides of proline, a feature encountered in nootropics, via the carboxylic group of ibuprofen, indomethacin, ketoprofen and naproxen were prepared. Proline carboxylic group was amidated or esterified with potential antioxidant or neuroprotective compounds. Proline was replaced by 4-hydroxyproline, 2-pipecolic acid or omitted, for investigating the contribution of structure to activity. Anti-inflammatory activity was determined, and selected compounds were examined for anti-dyslipidemic action, protection against brain ischaemia/reperfusion and brain penetration.Amides of proline and related structures with NSAIDs were synthesized. They were amidated or esterified with antioxidant or neuroprotective compounds. Activity against lipid peroxidation, inflammation and brain ischaemia was evaluated.