(S)-N-{3-[5-(4-fluorophenylmethyl)-thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea | 154355-79-0

• 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: (S)-N-{3-[5-(4-fluorophenylmethyl)-thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea
• 英文别名: (S)-N-{3-[5-(4-fluorophenylmethyl)-2-thienyl]-1-methyl-2-propynyl}-N-hydroxyurea；(S)-(-)-N-(3-{5-[(4-fluorophenyl)methyl]-2-thienyl}-1-methyl-2-propynyl)-N-hydroxyurea；(S)-(-)-N-{3-[5-(4-fluorobenzyl)thien-2-yl]-1-methylprop-2-ynyl}-N-hydroxyurea；1-[(2S)-4-[5-[(4-fluorophenyl)methyl]thiophen-2-yl]but-3-yn-2-yl]-1-hydroxyurea
• CAS: 154355-79-0
• 化学式: C₁₆H₁₅FN₂O₂S
• 分子量: 318.372
• InChiKey: MMSNEKOTSJRTRI-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  94.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(4-氟苄基)噻吩 在 双(乙腈)氯化钯(II) 、 N-碘代丁二酰亚胺 、 copper(l) iodide 、 溶剂黄146 、 二乙胺 、 三苯基膦 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 (S)-N-{3-[5-(4-fluorophenylmethyl)-thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea
  参考文献：
  名称：

  Preparation of (R)-(+)-N-[3-[5-[(4-Fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (ABT-761), a second-generation 5-lipoxygenase inhibitor.

  摘要：

  Structure-activity optimization of inhibitory potency and duration of action of N-hydroxyurea containing 5-lipoxygenase inhibitors was conducted. The lipophilic heteroaryl template and the link group connnecting the template to the N-hydroxyurea pharmacophore were modified. Inhibition of 5-lipoxygenase was evaluated in vitro in a human whole blood assay. An in vitro assay using liver microsomes from monkey was used to evaluate congeners for comparative rates of glucuronidation. (3-Heteroaryl-1-methyl-2-propynyl)-N-hydroxyureas were found to be more resistant to in vitro glucuronidation. The promising inhibitor N-[3-[5-(4-fluorophenoxy)2-furyl]-1-methyl-2-propynyl]-N-hydroxyurea (6) was found to have stereoselective glucuronidation in monkey and man. The R enantiomer 7 provided longer duration of inhibition as evaluated by an ex vivo whole blood assay. Further optimization of the lipophilic template led to the discovery of (R)-(+)-N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (11) with more effective and prolonged inhibition of leukotriene biosynthesis than zileuton (1) and 7 in monkey and man. The optimized 5-lipoxygenase inhibitor 11 was selected for development as an investigational drug for leukotriene-mediated disorders.

  DOI：

  10.1021/jm00024a004

文献信息

• Susceptibility gene for myocardial infarction, stroke, and PAOD; methods of treatment
  申请人：Helgadottir Anna

  公开号：US20050113408A1

  公开（公告）日：2005-05-26

  Linkage of myocardial infarction (MI) and a locus on chromosome 13q12 is disclosed. In particular, the FLAP gene within this locus is shown by genetic association analysis to be a susceptibility gene for MI and ACS, as well as stroke and PAOD. Pathway targeting for treatment and diagnostic applications in identifying those who are at risk of developing MI, ACS, stroke or PAOD, in particular are described.

  本研究揭示了心肌梗塞（MI）与染色体 13q12 上一个位点的联系。特别是，遗传关联分析表明，该基因座上的 FLAP 基因是心肌梗死和急性心肌梗死以及中风和 PAOD 的易感基因。该研究还描述了用于治疗和诊断的路径靶向技术，特别是用于识别有患心肌梗死、心肌梗死综合症、中风或急性心肌梗死综合症风险的人群。
• Susceptibility gene for myocardial infarction, stroke, and PAOD, methods of treatment
  申请人：Helgadottir Anna

  公开号：US20060019269A1

  公开（公告）日：2006-01-26

  Linkage of myocardial infarction (MI) and a locus on chromosome 13q12 is disclosed. In particular, the FLAP gene within this locus is shown by genetic association analysis to be a susceptibility gene for MI and ACS, as well as stroke and PAOD. Pathway targeting for treatment and diagnostic applications in identifying those who are at risk of developing MI, ACS, stroke or PAOD, in particular are described. The invention also provides for compositions comprising a leukotriene synthesis inhibitor and a stating and methods of using these compositions to reduce C-reactive protein in a human subject at risk of MI, ACS, stroke and/or PAOD.

  本研究揭示了心肌梗塞（MI）与染色体 13q12 上一个位点的联系。特别是，遗传关联分析表明，该基因座上的 FLAP 基因是心肌梗死和急性心肌梗死以及中风和 PAOD 的易感基因。本发明描述了用于治疗和诊断的靶向途径，特别是用于识别有患心肌梗死、心肌梗死综合症、中风或 PAOD 风险的人群。本发明还提供了包含白三烯合成抑制剂和说明的组合物，以及使用这些组合物降低有MI、ACS、中风和/或PAOD风险的人体内C反应蛋白的方法。
• SUBSTITUTED ARYLALKYNYL- AND HETEROARYLALKYNYL-N-HYDROXYUREA INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS
  申请人：ABBOTT LABORATORIES

  公开号：EP0667855A1

  公开（公告）日：1995-08-23
• EP0667855A4
  申请人：——

  公开号：EP0667855A4

  公开（公告）日：1996-02-21
• SUSCEPTIBILITY GENE FOR MYOCARDIAL INFARCTION; METHODS OF TREATMENT
  申请人：Decode Genetics EHF.

  公开号：EP1579010A2

  公开（公告）日：2005-09-28