苯乙酰胺,a-甲基-4-(2-甲基丙基)-,(S)- | 121839-78-9

• 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
• 中文名称: 苯乙酰胺,a-甲基-4-(2-甲基丙基)-,(S)-
• 英文名称: (2R)-2-[4-(2-methylpropyl)phenyl]propanamide
• 英文别名: (R)-2-(4-isobutylphenyl)propionamide；(R)-Ibuprofenamide
• CAS: 121839-78-9
• 化学式: C₁₃H₁₉NO
• 分子量: 205.3
• InChiKey: REUQKCDCQVNKLW-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 储存条件：
  存储条件：2-8°C，密封保存，并确保环境干燥。

制备方法与用途

生物活性 (-)-Ibuprofenamide 是 Ibuprofen（布洛芬）的酰胺前药，具有抗炎作用。Ibuprofen 可以抑制 COX-1 和 COX-2，其 IC50 值分别为 13 μM 和 370 μM，并展现出显著的抗炎活性。

靶点 COX-1, COX-2

反应信息

• 作为反应物：
  描述：

  苯乙酰胺,a-甲基-4-(2-甲基丙基)-,(S)- 在 三乙胺 、 三氯乙酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 生成 (R)-2-(4-isobutylphenyl)propanenitrile
  参考文献：
  名称：

  Retention of stereochemistry in the microwave assisted synthesis of 1H-tetrazole bioisosteric moiety from chiral phenyl-acetic acid derivatives

  摘要：

  Chiral substituted phenylethyl-1H-tetrazoles were built-up from the corresponding carboxylic acid derivatives by a useful three-step synthesis. The procedure, that preserves the chiral center from racemization, was successfully applied to a selection of several hit compounds by conversion of the carboxylic acid moiety to the nitrile derivatives and subsequent reaction with trimethylstannyl azide, under microwave conditions. A useful application to the corresponding tetrazole analogue has been found also in the conversion of the aminoacidic moiety like (R)-N-Cbz-phenylglycine showing a wide potential synthetic application. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.09.022
• 作为产物：
  描述：

  (R)-(-)-布洛芬 在 氯化亚砜 、 氨 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 生成 苯乙酰胺,a-甲基-4-(2-甲基丙基)-,(S)-
  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

• Microbial hydrolysis as a potent method for the preparation of optically active nitriles, amides and carboxylic acids
  作者：Hideaki Kakeya、Naoko Sakai、Takeshi Sugai、Hiromichi Ohta

  DOI：10.1016/s0040-4039(00)79663-8

  日期：1991.3

  Many kinds of aromatic nitriles have been hydrolyzed to afford the corresponding amides and carboxylic acids, by the aid of enzyme system of Rhodococcus butanica. This enzymatic hydrolysis can be successfully applied to the kinetic resolution of α-arylpropionitriles, resulting in the formation of (R)-amides and (S)-carboxylic acids.

  借助于丁酸红球菌的酶系统，已经将多种芳族腈水解成相应的酰胺和羧酸。该酶促水解可成功地应用于α-芳基丙腈的动力学拆分，从而导致形成（R）-酰胺和（S）-羧酸。
• Amides, useful in the inhibition of il-8-induced chemotaxis of neutrophils
  申请人：——

  公开号：US20040181073A1

  公开（公告）日：2004-09-16

  N-(2-aryl-propionyl)-amides of formula (I) are described. 1 The process for their preparation and pharmaceutical preparations thereof are also described. The amides of the invention are useful in the prevention and treatment of tissue damage due to the exacerbate recruitment of polymorphonuclear neutrophils (leukocytes PMN) at the inflammatory sites. In particular, the invention relates to the R enantiomers of N-(2-aryl-propionyl)amides of formula (I) for use in the ihibition of the chemotaxis of neutrophils induced by IL-8. The compounds of the invention are used in the treatment of psoriasis, ulcerative cholitis, glomerular nephritis, acute respiratory insufficiency, idiopathic fibrosis, and rheumatoid arthritis.

  公式（I）的N-（2-芳基丙酰基）酰胺已被描述。还描述了它们的制备过程和药物制剂。本发明的酰胺在预防和治疗由于在炎症部位加重多形核中性粒细胞（白细胞PMN）的招募而导致的组织损伤方面是有用的。具体而言，本发明涉及用于抑制IL-8诱导的中性粒细胞趋化作用的N-（2-芳基丙酰基）酰胺的R对映体。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、特发性纤维化和类风湿关节炎。
• N - ( 2 - aryl - propionyl ) - sulfonamides and pharmaceutical preparations containing them
  申请人：Dompe S.p.A.

  公开号：US20030216392A1

  公开（公告）日：2003-11-20

  The compounds of formula 1, 1 wherein R and R 2 are as defined in the disclosure, are useful in the prevention and treatment of tissue damage due to exacerbated recruitment of polymorphonuclear neutrophils (PMN leukocytes) at the inflammatory sites.

  式1，1中R和R2的化合物如披露所述，对于预防和治疗由于在炎症部位加重的多形核中性粒细胞（PMN白细胞）的招募而引起的组织损伤是有用的。
• [EN] N-(2-ARYL-PROPIONYL)-SULFONAMIDES AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM<br/>[FR] N-(2-ARYL-PROPIONYL)-SULFAMIDES ET PREPARATIONS PHARMACEUTIQUES CONTENANT CES DERNIERS
  申请人：DOMPE SPA

  公开号：WO2000024710A1

  公开（公告）日：2000-05-04

  The compounds of formula (1), wherein R and R2 are as defined in the disclosure, are useful in the prevention and treatment of tissue damage due to exacerbated recruitment of polymorphonuclear neutrophils (PMN leukocytes) at the inflammatory sites.

  式（1）中的化合物，其中R和R2如所述定义的那样，对于预防和治疗由于炎症部位过度招募多形核中性粒细胞（PMN白细胞）引起的组织损伤是有用的。
• 2-Arylpropionic Acid Derivatives and Pharmaceutical Compositions Containing Them
  申请人：Allegretti Marcello

  公开号：US20080312293A1

  公开（公告）日：2008-12-18

  The present invention relates to selected (R)-2-phenyl-propionamides and (R)-2-phenyl-sulfonamides with a hydrogen bond acceptor atom/group in a well defined position in the chemical space. These compounds show a surprising potent inhibitory effect on C5a induced human PMN chemotaxis. The compounds of the invention absolutely lack of CXCL8 inhibitory activity. Said compounds are useful in the treatment of pathologies depending on the chemotactic activation of neutrophils and monocytes induced by the fraction C5a of the complement. In particular, the compounds of the invention are useful in the treatment of sepsis, psoriasis, rheumatoid arthritis, ulcerative colitis, acute respiratory distress syndrome, idiopathic fibrosis, glomerulonephritis and in the prevention and treatment of injury caused by ischemia and reperfusion.

  本发明涉及在化学空间中具有氢键受体原子/基团的选定（R）-2-苯基-丙酰胺和（R）-2-苯基-磺酰胺。这些化合物表现出惊人的强烈抑制C5a诱导的人类PMN趋化性的效果。本发明的化合物绝对缺乏CXCL8抑制活性。所述化合物在治疗与补体C5a诱导的中性粒细胞和单核细胞趋化活化有关的病理过程中有用。特别是，在治疗败血症、牛皮癣、类风湿性关节炎、溃疡性结肠炎、急性呼吸窘迫综合征、特发性纤维化、肾小球肾炎以及缺血再灌注损伤的预防和治疗方面，本发明的化合物非常有用。