5-(4-butoxyphenyl)pentanoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(4-butoxyphenyl)pentanoic acid
• 化学式: C₁₅H₂₂O₃
• 分子量: 250.338
• InChiKey: VNNLNGKWPSCMQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-butoxyphenyl)pentanoic acid 在 盐酸羟胺 、 sodium ethanolate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 5-(4-butoxyphenyl)-N-(4-(2-(hydroxyamino)-2-oxoethyl)phenyl)pentanamide
  参考文献：
  名称：

  Hydroxamic Acids Constitute a Novel Class of Autotaxin Inhibitors that Exhibit in Vivo Efficacy in a Pulmonary Fibrosis Model

  摘要：

  Autotaxin (ATX) catalyzes the hydrolysis of lysophosphatidylcholine (LPC) generating the lipid mediator lysophosphatidic acid (LPA). Both ATX and LPA are involved in various pathological inflammatory conditions, including fibrosis and cancer, and have attracted great interest as medicinal targets over the past decade. Thus, the development of novel potent ATX inhibitors is of great importance. We have developed a novel class of ATX inhibitors containing the zinc binding functionality of hydroxamic acid. Such novel hydroxamic acids that incorporate a non-natural delta-amino acid residue exhibit high in vitro inhibitory potency over ATX (IC50 values 50-60 nM). Inhibitor 32, based on delta-norleucine, was tested for its efficacy in a mouse model of pulmonary inflammation and fibrosis induced by bleomycin and exhibited promising efficacy. The novel hydroxamic ATX inhibitors provide excellent tools for the study of the role of the enzyme and could contribute to the development of novel therapeutic agents for the treatment of fibrosis and other chronic inflammatory diseases.

  DOI：

  10.1021/acs.jmedchem.8b00232
• 作为产物：
  描述：

  4-丁氧基苯甲醛 在 palladium 10% on activated carbon 、 氢气 、 sodium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 36.0h， 生成 5-(4-butoxyphenyl)pentanoic acid
  参考文献：
  名称：

  Hydroxamic Acids Constitute a Novel Class of Autotaxin Inhibitors that Exhibit in Vivo Efficacy in a Pulmonary Fibrosis Model

  摘要：

  Autotaxin (ATX) catalyzes the hydrolysis of lysophosphatidylcholine (LPC) generating the lipid mediator lysophosphatidic acid (LPA). Both ATX and LPA are involved in various pathological inflammatory conditions, including fibrosis and cancer, and have attracted great interest as medicinal targets over the past decade. Thus, the development of novel potent ATX inhibitors is of great importance. We have developed a novel class of ATX inhibitors containing the zinc binding functionality of hydroxamic acid. Such novel hydroxamic acids that incorporate a non-natural delta-amino acid residue exhibit high in vitro inhibitory potency over ATX (IC50 values 50-60 nM). Inhibitor 32, based on delta-norleucine, was tested for its efficacy in a mouse model of pulmonary inflammation and fibrosis induced by bleomycin and exhibited promising efficacy. The novel hydroxamic ATX inhibitors provide excellent tools for the study of the role of the enzyme and could contribute to the development of novel therapeutic agents for the treatment of fibrosis and other chronic inflammatory diseases.

  DOI：

  10.1021/acs.jmedchem.8b00232

文献信息

• US5998642A
  申请人：——

  公开号：US5998642A

  公开（公告）日：1999-12-07
• US6001869A
  申请人：——

  公开号：US6001869A

  公开（公告）日：1999-12-14
• US6025511A
  申请人：——

  公开号：US6025511A

  公开（公告）日：2000-02-15
• US6048989A
  申请人：——

  公开号：US6048989A

  公开（公告）日：2000-04-11
• [EN] MMP INHIBITOR<br/>[FR] INHIBITEUR DE MMP
  申请人：YAKULT HONSHA KK

  公开号：WO2009113320A1

  公开（公告）日：2009-09-17

  　優れたＭＭＰ阻害効果を有し、かつ、副作用が軽減された新規な化合物を提供する。 　一般式（１） （式中、Ｒ１は（Ｅ）－３－フェニルアリル基又は３－フェニルプロピル基を示し； Ｒ２は、水素原子、イソブチル基、２－（４－メトキシフェニル）エチル基等を示し； Ｒ３は１Ｈ－インドール－３－イル基、１－ナフチル基等を示し； Ｒ４は、メチル基、ベンジルオキシ基、ヒドロキシ基、フェネチル基等を示す。 で表されるヒドロキサム酸誘導体又はその塩を有効成分とするマトリックスメタロプロテアーゼ阻害剤。