5-(4-butoxyphenyl)-N-(4-(2-(hydroxyamino)-2-oxoethyl)phenyl)pentanamide

• 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-butoxyphenyl)-N-(4-(2-(hydroxyamino)-2-oxoethyl)phenyl)pentanamide
• 英文别名: 5-(4-butoxyphenyl)-N-[4-[2-(hydroxyamino)-2-oxoethyl]phenyl]pentanamide
• 化学式: C₂₃H₃₀N₂O₄
• 分子量: 398.502
• InChiKey: YVMJJSVMOXPMCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-丁氧基苯甲醛 在 palladium 10% on activated carbon 、 盐酸羟胺 、 氢气 、 sodium ethanolate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 36.0h， 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

文献信息

• [EN] AUTOTAXIN INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS D'AUTOTAXINE ET LEURS UTILISATIONS
  申请人：NAT AND KAPODISTRIAN UNIV OF ATHENS

  公开号：WO2016184561A1

  公开（公告）日：2016-11-24

  Novel inhibitors of the enzyme autotaxin are described. The inhibitors contain one or two zinc-binding groups at the appropriate distance, Also described are uses thereof, such as for the inhibition of autotaxin activity and the treatment of various conditions (e.g., inflammatory conditions, cancer, obesity, autoimmune diseases).

  本文描述了一种自体脂肪酸酯酶的新型抑制剂。这些抑制剂包含一个或两个适当距离的锌结合基团。此外，还描述了这些抑制剂的用途，例如用于抑制自体脂肪酸酯酶的活性和治疗各种疾病（例如炎症性疾病、癌症、肥胖症、自身免疫性疾病）。
• AUTOTAXIN INHIBITORS AND USES THEREOF
  申请人：NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS

  公开号：US20180141965A1

  公开（公告）日：2018-05-24

  Novel inhibitors of the enzyme autotaxin are described. The inhibitors contain one or two zinc-binding groups at the appropriate distance, Also described are uses thereof, such as for the inhibition of autotaxin activity and the treatment of various conditions (e.g., inflammatory conditions, cancer, obesity, autoimmune diseases).
• 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.