(R)-N-[2-(2-Hydroxy-ethoxy)-ethyl]-2-(4-isobutyl-phenyl)-propionamide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (R)-N-[2-(2-Hydroxy-ethoxy)-ethyl]-2-(4-isobutyl-phenyl)-propionamide
• 英文别名: (2R)-N-[2-(2-hydroxyethoxy)ethyl]-2-[4-(2-methylpropyl)phenyl]propanamide
• 化学式: C₁₇H₂₇NO₃
• 分子量: 293.406
• InChiKey: VOIIYDOOICJRII-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (R)-(-)-布洛芬 在 氯化亚砜 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (R)-N-[2-(2-Hydroxy-ethoxy)-ethyl]-2-(4-isobutyl-phenyl)-propionamide
  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-Aryl-acetic acids, their derivatives and pharmaceutical compositions containing them
  申请人：Moriconi Alessio

  公开号：US20060223842A1

  公开（公告）日：2006-10-05

  Selected 2-arylacetic acids, their derivatives and pharmaceutical compositions that contain these compounds are useful in inhibiting chemotactic activation of neutrophils (PMN leukocytes) induced by the interaction of Interleukin-8 (IL-8) with CXCR1 and CXCR2-membrane receptors. The compounds are used for the prevention and treatment of pathologies deriving from said activation. In particular, 2(ortho)-substituted arylacetic acids or their derivatives, such as amides and sulfonamides, lack cyclo-oxygenase inhibition activity and are particularly useful in the treatment of neutrophil-dependent pathologies such as psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and in the prevention and treatment of damages caused by ischemia and reperfusion.

  选择的2-芳基乙酸及其衍生物和包含这些化合物的药物组合物对于抑制由白细胞介素-8（IL-8）与CXCR1和CXCR2膜受体相互作用引起的嗜中性粒细胞（PMN白细胞）趋化活化非常有用。这些化合物用于预防和治疗由该活化引起的病理。特别是2（邻）-取代芳基乙酸或其衍生物，例如酰胺和磺酰胺，缺乏环氧合酶抑制活性，特别适用于治疗嗜中性粒细胞依赖性病理，如银屑病、溃疡性结肠炎、黑色素瘤、慢性阻塞性肺疾病（COPD）、大疱性类天疱疮、类风湿性关节炎、特发性纤维化、肾小球肾炎以及缺血再灌注引起的损伤的预防和治疗。
• 2-ARYL-ACETIC ACIDS, THEIR DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：MORICONI Alessio

  公开号：US20110195967A1

  公开（公告）日：2011-08-11

  Selected 2-arylacetic acids, their derivatives and pharmaceutical compositions that contain these compounds are useful in inhibiting chemotactic activation of neutrophils (PMN leukocytes) induced by the interaction of Interleukin-8 (IL-8) with CXCR1 and CXCR2 membrane receptors. The compounds are used for the prevention and treatment of pathologies deriving from their activation. In particular, 2(ortho)-substituted arylacetic acids or their derivatives, such as amides and sulfonamides, lack cyclo-oxygenase inhibition activity and are particularly useful in the treatment of neutrophil-dependent pathologies such as psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and in the prevention and treatment of damages caused by ischemia and reperfusion.

  选定的2-芳基乙酸及其衍生物和包含这些化合物的制药组合物可用于抑制由白细胞介素8（IL-8）与CXCR1和CXCR2膜受体相互作用引起的中性粒细胞（PMN白细胞）的趋化激活。这些化合物用于预防和治疗由其激活引起的病理状况。特别是2-（邻）取代芳基乙酸或其衍生物，如酰胺和磺酰胺，缺乏环氧化酶抑制活性，特别适用于治疗中性粒细胞依赖性病理状况，如银屑病，溃疡性结肠炎，黑色素瘤，慢性阻塞性肺疾病（COPD），大疱性天疱病，类风湿性关节炎，特发性纤维化，肾小球肾炎以及预防和治疗缺血再灌注引起的损伤。
• 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.
• US7776909B2
  申请人：——

  公开号：US7776909B2

  公开（公告）日：2010-08-17
• US8648110B2
  申请人：——

  公开号：US8648110B2

  公开（公告）日：2014-02-11