(2R)-2-[4-(2-methylpropyl)phenyl]-N-pyrimidin-4-ylpropanamide

• 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: (2R)-2-[4-(2-methylpropyl)phenyl]-N-pyrimidin-4-ylpropanamide
• 化学式: C₁₇H₂₁N₃O
• 分子量: 283.373
• InChiKey: IQZSZBLUQFJZNG-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-氨基嘧啶 、 (R)-(-)-布洛芬 在 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以60%的产率得到(2R)-2-[4-(2-methylpropyl)phenyl]-N-pyrimidin-4-ylpropanamide
  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

• Substituted alkylamine derivatives and methods of use
  申请人：Amgen Inc.

  公开号：US20030225106A1

  公开（公告）日：2003-12-04

  Selected amines are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  选定的胺对预防治疗疾病有效，如血管生成介导的疾病。本发明包括新的化合物、类似物、前药和药用可接受的盐，药物组合物和预防治疗疾病和其他疾病或状况的方法，包括癌症等。本发明还涉及制造这类化合物的过程以及在此类过程中有用的中间体。
• (R)-2-ARYL-PROPIONAMIDES, USEFUL IN THE INHIBITION OF IL-8 INDUCED CHEMIOTAXIS OF NEUTROPHILS
  申请人：DOMPE' pha.r.ma S.p.A.

  公开号：EP1255726B1

  公开（公告）日：2009-11-11
• SUBSTITUTED 2-ALKYLAMINE NICOTINIC AMIDE DERIVATIVES AND USE THERE OF
  申请人：AMGEN INC.

  公开号：EP1537084B1

  公开（公告）日：2013-08-21
• US6878714B2
  申请人：——

  公开号：US6878714B2

  公开（公告）日：2005-04-12
• US7687643B2
  申请人：——

  公开号：US7687643B2

  公开（公告）日：2010-03-30