5-[(4-fluorobenzoyl)amino]pentanoic acid

• 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: 5-[(4-fluorobenzoyl)amino]pentanoic acid
• 英文别名: Pentanoic acid, 5-[(4-fluorobenzoyl)amino]-
• 化学式: C₁₂H₁₄FNO₃
• 分子量: 239.246
• InChiKey: BDROKDOQKWRLRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-[(4-fluorobenzoyl)amino]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 4-fluoro-N-(5-((4-(2-(hydroxyamino)-2-oxoethyl)phenyl)amino)-5-oxopentyl)benzamide
  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：

  5-氨基戊酸乙酯 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 5-[(4-fluorobenzoyl)amino]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

• ウレア誘導体化合物、これを含有する放射性医薬
  申请人：国立大学法人京都大学

  公开号：JP2015089881A

  公开（公告）日：2015-05-11

  【課題】フッ素基を有しつつ、前立腺特異的膜抗原（ＰＳＭＡ）への親和性が維持又は向上された、ウレア誘導体化合物を提供する。【解決手段】下記式（１）：【化１】（式（１）中、ｍは０又は１、ｎは１〜４の整数、Ｒは水素又はカルボキシル基、Ｆは非放射性フッ素又は放射性フッ素を示す。）で表わされるウレア誘導体化合物又はその塩、及び、上記化合物又はその塩（但し、式（１）中、Ｆは放射性フッ素）を含有する、放射性医薬。【選択図】なし

  题目：提供具有氟基且保持或提高对前列腺特异性膜抗原（PSMA）亲和性的尿素衍生物化合物。 解决方案：以下式（1）： [化1] （其中，m为0或1，n为1至4的整数，R为氢或羧基，F表示非放射性氟或放射性氟。）表示的尿素衍生物化合物或其盐，以及含有上述化合物或其盐（但在式（1）中，F为放射性氟）的放射性药物。 选择图：无。
• Hydroxamic Acids Constitute a Novel Class of Autotaxin Inhibitors that Exhibit <i>in Vivo</i> Efficacy in a Pulmonary Fibrosis Model
  作者：Aikaterini Nikolaou、Ioanna Ninou、Maroula G. Kokotou、Eleanna Kaffe、Antreas Afantitis、Vassilis Aidinis、George Kokotos

  DOI：10.1021/acs.jmedchem.8b00232

  日期：2018.4.26

  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.