(R)-2-[(3-benzoyl)phenyl]-N-[3-(dimethylamino)propyl]propionamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-2-[(3-benzoyl)phenyl]-N-[3-(dimethylamino)propyl]propionamide
• 英文别名: R(-)-2-[(3-benzoyl)phenyl]-N-[3-(N',N'-dimethylamino)propyl]propionamide；(2R)-2-(3-benzoylphenyl)-N-[3-(dimethylamino)propyl]propanamide
• 化学式: C₂₁H₂₆N₂O₂
• 分子量: 338.45
• InChiKey: XIXBLWPVLFFQJU-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (2R)-2-(3-苯甲酰基苯基)丙酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 生成 (R)-2-[(3-benzoyl)phenyl]-N-[3-(dimethylamino)propyl]propionamide
  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

文献信息

• Quaternary ammonium salts of omega-aminoalkylamides of r-2-aryl-propionic acids and pharmaceutical compositions containing them
  申请人：——

  公开号：US20040266870A1

  公开（公告）日：2004-12-30

  (R)-Enantiomers of quaternary ammonium salts of general formula (I) are described: 1 where R, R 1 , R 2 , R 3 , X and Z are as defined in the description. The process for their preparation and pharmaceutical preparations thereof are also described. The quaternary salts of the invention are useful in the inhibition of chemotaxis of neutrophils and monocytes induced by the fraction C 5 a of the complement and are used in the treatment of psoriasis, pemphigus and pemphigoid, rheumatoid arthritis, intestinal chronic inflammatory pathologies including ulcerative colitis, acute respiratory distress syndrome, idiopathic fibrosis, cystic fibrosis, chronic obstructive pulmonary disease and glomerulonephritis. The compounds of the invention are advantageously used in the prevention and the treatment of injury caused by ischemia and reperfusion.

  通用公式(I)的(R)-对映体的季铵盐被描述：其中R、R1、R2、R3、X和Z如描述中所定义。还描述了它们的制备过程和药物制剂。本发明的季铵盐在抑制由补体C5a分数诱导的中性粒细胞和单核细胞趋化方面具有用途，并用于治疗牛皮癣、天疱疮和天疱疮、类风湿关节炎、包括溃疡性结肠炎、急性呼吸窘迫综合征、特发性纤维化、囊性纤维化、慢性阻塞性肺病和肾小球肾炎在内的肠道慢性炎症病变。本发明的化合物有利地用于预防和治疗缺血再灌注引起的损伤。
• Omega aminoalkylamides of R-2 aryl propionic acids as inhibitors of the chemotaxis of polymorphonucleate and mononucleate cells
  申请人：Allegretti Marcello

  公开号：US20050080067A1

  公开（公告）日：2005-04-14

  (R)-2-Arylpropionamide compounds of formula (I) are described. The process for their preparation and pharmaceutical preparations thereof are also described. The 2-Arylpropionamides of the invention are useful in the prevention and treatment of tissue damage due to the exacerbate recruitment of polymorphonuclear leukocytes (leukocytes PMN) and of monocytes at the inflammatory sites. In particular, the invention relates to the R enantiomers of omega-aminoalkylamides of 2-aryl propionic acids, of formula (I), for use in the inhibition of the chemotaxis of neutrophils and monocytes induced by the C5a fraction of the complement and by other chemotactic proteins whose biological activity is associated with activation of a 7-TD receptor. Selected compounds of formula (I) are dual inhibitors of both the C5a-induced chemotaxis of neutrophils and monocytes and the IL-8-induced chemotaxis of PMN leukocytes. The compounds of the invention are used in the treatment of psoriasis, ulcerative cholitis, glomerular nephritis, acute respiratory insufficiency, idiopathic fibrosis, rheumatoid arthritis and in the prevention and the treatment of injury caused by ischemia and reperfusion.

  本文描述了化合物公式(I)的(R)-2-Arylpropionamide化合物，以及它们的制备过程和制药制剂。发明的2-Arylpropionamides可用于预防和治疗由于炎症部位的多形核白细胞（白细胞PMN）和单核细胞的加重招募而导致的组织损伤。特别地，本发明涉及公式(I)的2-aryl丙酸的ω-氨基烷基酰胺的R对映体，用于抑制由补体的C5a分数和其他趋化蛋白引起的中性粒细胞和单核细胞趋化，并且这些趋化蛋白的生物活性与7-TD受体的激活有关。公式(I)的选定化合物是同时抑制C5a诱导的中性粒细胞和单核细胞趋化以及IL-8诱导的PMN白细胞趋化的双重抑制剂。本发明的化合物用于治疗牛皮癣、溃疡性结肠炎、肾小球肾炎、急性呼吸功能不全、特发性纤维化、类风湿性关节炎以及预防和治疗缺血再灌注引起的损伤。
• OMEGA-AMINOALKYLAMIDES OF R-2-ARYL-PROPIONIC ACIDS AS INHIBITORS OF THE CHEMOTAXIS OF POLYMORPHONUCLEATE AND MONONUCLEATE CELLS
  申请人：ALLEGRETTI Marcello

  公开号：US20080045522A1

  公开（公告）日：2008-02-21

  (R)-2-Arylpropionamide compounds of formula (I) are described. The process for their preparation and pharmaceutical preparations thereof are also described. The 2-Arylpropionamides of the invention are useful in the prevention and treatment of tissue damage due to the exacerbate recruitment of polymorphonuclear leukocytes (leukocytes PMN) and of monocytes at the inflammatory sites. In particular, the invention relates to the R enantiomers of omega-aminoalkylamides of 2-aryl propionic acids, of formula (I), for use in the inhibition of the chemotaxis of neutrophils and monocytes induced by the C5a fraction of the complement and by other chemotactic proteins whose biological activity is associated with activation of a 7-TD receptor. Selected compounds of formula (I) are dual inhibitors of both the C5a-induced chemotaxis of neutrophils and monocytes and the IL-8-induced chemotaxis of PMN leukocytes. The compounds of the invention are used in the treatment of psoriasis, ulcerative cholitis, glomerular nephritis, acute respiratory insufficiency, idiopathic fibrosis, rheumatoid arthritis and in the prevention and the treatment of injury caused by ischemia and reperfusion.

  本文描述了公式(I)的(R)-2-芳基丙酰胺化合物，以及它们的制备过程和制药制剂。本发明中的2-芳基丙酰胺类化合物可用于预防和治疗由于在炎症部位诱导多形核白细胞（白细胞PMN）和单核细胞的加重招募而导致的组织损伤。特别是，本发明涉及公式(I)的ω-氨基烷基酰胺的R对映体，用于抑制由C5a补体分数和其他趋化蛋白诱导的中性粒细胞和单核细胞趋化，其生物活性与7-TD受体的激活有关。公式(I)的某些选择性化合物是同时抑制C5a诱导的中性粒细胞和单核细胞趋化以及IL-8诱导的PMN白细胞趋化的双重抑制剂。本发明中的化合物用于治疗牛皮癣、溃疡性结肠炎、肾小球肾炎、急性呼吸功能不全、特发性纤维化、类风湿关节炎以及预防和治疗缺血再灌注所致的损伤。
• "OMEGA-AMINOALKYLAMIDES OF R-2-ARYL-PROPIONIC ACIDS AS INHIBITORS OF THE CHEMOTAXIS OF POLYMORPHONUCLEATE AND MONONUCLEATE CELLS"
  申请人：Dompé S.p.A.

  公开号：US20130079514A1

  公开（公告）日：2013-03-28

  (R)-2-Arylpropionamide compounds of formula (I), pharmaceutical preparations of the compounds and a process for making the compounds are described. The 2-Arylpropionamides of the invention are useful in the prevention and treatment of tissue damage due to the exacerbated recruitment of polymorphonuclear leukocytes and monocytes at inflammatory sites. In particular, the invention relates to the R enantiomers of omega-aminoalkylamides of 2-aryl propionic acids, of formula (I), for use as inhibitors of chemotaxis of neutrophils and monocytes induced by the C5a fraction of complement and by other chemotactic proteins whose biological activity is associated with activation of a 7-TD receptor. Selected compounds of formula (I) are dual inhibitors of both the C5a-induced chemotaxis of neutrophils and monocytes and the IL-8-induced chemotaxis of polymorphonuclear leukocytes.

  本文描述了式(I)的(R)-2-Arylpropionamide化合物、该化合物的制药制剂以及制备该化合物的方法。本发明中的2-Arylpropionamides可用于预防和治疗由于在炎症部位过度招募多形核白细胞和单核细胞而引起的组织损伤。特别地，本发明涉及公式(I)的omega-氨基烷基酰胺的R对映体，用作抑制与激活7-TD受体相关的C5a补体分数和其他趋化蛋白引起的中性粒细胞和单核细胞趋化的抑制剂。公式(I)的选定化合物是同时抑制C5a诱导的中性粒细胞和单核细胞趋化以及IL-8诱导的多形核白细胞趋化的双重抑制剂。
• OMEGA-AMINOALKYLAMIDES OF (R)-2-ARYL-PROPIONIC ACIDS AS INHIBITORS OF THE CHEMOTAXIS OF POLYMORPHONUCLEATE AND MONONUCLEATE CELLS
  申请人：Dompé farmaceutici s.p.a.

  公开号：EP1366018B1

  公开（公告）日：2016-07-06