(S)-2-[(R)-2-(4-isobutylphenyl)propionylamino]propionic acid methyl ester | 354899-91-5

• 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)-2-[(R)-2-(4-isobutylphenyl)propionylamino]propionic acid methyl ester
• 英文别名: methyl (2S)-2-[[(2R)-2-[4-(2-methylpropyl)phenyl]propanoyl]amino]propanoate
• CAS: 354899-91-5
• 化学式: C₁₇H₂₅NO₃
• 分子量: 291.39
• InChiKey: FTIROIWXFBLQRE-OLZOCXBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-[(R)-2-(4-isobutylphenyl)propionylamino]propionic acid methyl ester 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 以95%的产率得到(S)-2-[(R)-2-(4-Isobutyl-phenyl)-propionylamino]-propionic acid
  参考文献：
  名称：

  2-Arylpropionic CXC Chemokine Receptor 1 (CXCR1) Ligands as Novel Noncompetitive CXCL8 Inhibitors

  摘要：

  The CXC chemokine CXCL8/IL-8 plays a major role in the activation and recruitment of polymorphonuclear (PMN) cells at inflammatory sites. CXCL8 activates PMNs by binding the seven-transmembrane (7-TM) G-protein-coupled receptors CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2). (R)-Ketoprofen (1) was previously reported to be a potent and specific noncompetitive inhibitor of CXCL8-induced human PMNS chemotaxis. We report here molecular modeling studies showing a putative interaction site of 1 in the TM region of CXCR1. The binding model was confirmed by alanine scanning mutagenesis and photoaffinity labeling experiments. The molecular model driven medicinal chemistry optimization of 1 led to a new class of potent and specific inhibitors of CXCL8 biological activity. Among these, repertaxin (13) was selected as a clinical candidate drug for prevention of post-ischemia reperfusion injury.

  DOI：

  10.1021/jm049082i
• 作为产物：
  描述：

  (R)-(-)-布洛芬 在 氯化亚砜 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (S)-2-[(R)-2-(4-isobutylphenyl)propionylamino]propionic acid methyl ester
  参考文献：
  名称：

  Predicting Human Serum Albumin Affinity of Interleukin-8 (CXCL8) Inhibitors by 3D-QSPR Approach

  摘要：

  A novel class of 2-(R)-phenylpropionamides has been recently reported to inhibit in vitro and in vivo interleukin-8 (CXCL8)-induced biological activities, These CXCL8 inhibitors are derivatives of phenylpropionic nonsteroidal antiinflammatory drugs (NSAIDs), high-affinity ligands for site II of human serum albumin (HSA). Up to date, only a limited number of in silico models for the prediction of albumin protein binding are available. A three-dimensional quantitative structure-property relationship (3D-QSPR) approach was used to model the experimental affinity constant (K-i) to plasma proteins of 37 structurally related molecules, using physicochemical. and 3D-pharmacophoric descriptors. Molecular docking studies highlighted that training set molecules preferentially bind site II of HSA. The obtained model shows satisfactory statistical parameters both in fitting and predicting validation. External validation confirmed the statistical significance of the chemometric model, which is a powerful tool for the prediction of HSA binding in virtual libraries of structurally related compounds.

  DOI：

  10.1021/jm049227l

文献信息

• 2-Arylpropionic CXC Chemokine Receptor 1 (CXCR1) Ligands as Novel Noncompetitive CXCL8 Inhibitors
  作者：Marcello Allegretti、Riccardo Bertini、Maria Candida Cesta、Cinzia Bizzarri、Rosa Di Bitondo、Vito Di Cioccio、Emanuela Galliera、Valerio Berdini、Alessandra Topai、Giuseppe Zampella、Vincenzo Russo、Nicoletta Di Bello、Giuseppe Nano、Luca Nicolini、Massimo Locati、Piercarlo Fantucci、Saverio Florio、Francesco Colotta

  DOI：10.1021/jm049082i

  日期：2005.6.1

  The CXC chemokine CXCL8/IL-8 plays a major role in the activation and recruitment of polymorphonuclear (PMN) cells at inflammatory sites. CXCL8 activates PMNs by binding the seven-transmembrane (7-TM) G-protein-coupled receptors CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2). (R)-Ketoprofen (1) was previously reported to be a potent and specific noncompetitive inhibitor of CXCL8-induced human PMNS chemotaxis. We report here molecular modeling studies showing a putative interaction site of 1 in the TM region of CXCR1. The binding model was confirmed by alanine scanning mutagenesis and photoaffinity labeling experiments. The molecular model driven medicinal chemistry optimization of 1 led to a new class of potent and specific inhibitors of CXCL8 biological activity. Among these, repertaxin (13) was selected as a clinical candidate drug for prevention of post-ischemia reperfusion injury.
• Predicting Human Serum Albumin Affinity of Interleukin-8 (CXCL8) Inhibitors by 3D-QSPR Approach
  作者：Loretta Aureli、Gabriele Cruciani、Maria Candida Cesta、Roberto Anacardio、Lucio De Simone、Alessio Moriconi

  DOI：10.1021/jm049227l

  日期：2005.4.1

  A novel class of 2-(R)-phenylpropionamides has been recently reported to inhibit in vitro and in vivo interleukin-8 (CXCL8)-induced biological activities, These CXCL8 inhibitors are derivatives of phenylpropionic nonsteroidal antiinflammatory drugs (NSAIDs), high-affinity ligands for site II of human serum albumin (HSA). Up to date, only a limited number of in silico models for the prediction of albumin protein binding are available. A three-dimensional quantitative structure-property relationship (3D-QSPR) approach was used to model the experimental affinity constant (K-i) to plasma proteins of 37 structurally related molecules, using physicochemical. and 3D-pharmacophoric descriptors. Molecular docking studies highlighted that training set molecules preferentially bind site II of HSA. The obtained model shows satisfactory statistical parameters both in fitting and predicting validation. External validation confirmed the statistical significance of the chemometric model, which is a powerful tool for the prediction of HSA binding in virtual libraries of structurally related compounds.