ethyl 4-(5-(((4-acetoxybenzyl)oxy)amino)-2-(ethoxycarbonyl)-5-oxopentyl)benzoate

• 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: ethyl 4-(5-(((4-acetoxybenzyl)oxy)amino)-2-(ethoxycarbonyl)-5-oxopentyl)benzoate
• 英文别名: Ethyl 4-[5-[(4-acetyloxyphenyl)methoxyamino]-2-ethoxycarbonyl-5-oxopentyl]benzoate；ethyl 4-[5-[(4-acetyloxyphenyl)methoxyamino]-2-ethoxycarbonyl-5-oxopentyl]benzoate
• 化学式: C₂₆H₃₁NO₈
• 分子量: 485.534
• InChiKey: LPANGVCMKDFBSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  35
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  乙酸对甲酚酯 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 氯甲酸乙酯 、 sodium hydride 、 三乙胺 、 肼 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.67h， 生成 ethyl 4-(5-(((4-acetoxybenzyl)oxy)amino)-2-(ethoxycarbonyl)-5-oxopentyl)benzoate
  参考文献：
  名称：

  [EN] PRODRUGS OF HYDROXAMATE-BASED GCPII INHIBITORS
  [FR] PROMÉDICAMENTS D'INHIBITEURS DE GCPII À BASE D'HYDROXAMATE

  摘要：

  本发明揭示了羟肟基GCPII抑制剂的前药及其用于治疗疾病或病况的方法。

  公开号：

  WO2018094334A1

文献信息

• Prodrug compositions and utility of hydroxamate-based GCPII inhibitors
  申请人：The Johns Hopkins University

  公开号：US11059775B2

  公开（公告）日：2021-07-13

  Prodrugs of hydroxamate-based GCPII inhibitors and methods of their use for treating a disease or condition are disclosed.

  本发明公开了羟基氨基甲酸酯类 GCPII 抑制剂的原药及其用于治疗疾病或病症的方法。
• Discovery of a <i>para</i>-Acetoxy-benzyl Ester Prodrug of a Hydroxamate-Based Glutamate Carboxypeptidase II Inhibitor as Oral Therapy for Neuropathic Pain
  作者：Rana Rais、Jan Vávra、Tomáš Tichý、Ranjeet P. Dash、Alexandra J. Gadiano、Lukáš Tenora、Lenka Monincová、Cyril Bařinka、Jesse Alt、Sarah C. Zimmermann、C. Ethan Slusher、Ying Wu、Krystyna Wozniak、Pavel Majer、Takashi Tsukamoto、Barbara S. Slusher

  DOI：10.1021/acs.jmedchem.7b00825

  日期：2017.9.28

  4-Carboxy-alpha-[3-(hydroxyamino)-3-oxopropyl]-benzenepropanoic acid 1 is a potent hydroxamate-based inhibitor of glutamate carboxypeptidase II. In an attempt to improve its poor oral pharmacokinetics, we synthesized a series of prodrugs by masking its hydrophilic hydroxamate group. Prodrugs were evaluated for oral availability in mice and showed varying degree of plasma exposure to 1. Of these, para-acetoxybenzyl-based, 4-(5-(((4-acetoxybenzyl)oxy)amino)-2-carboxy-5-oxopentyl)benzoic acid, 12, provided 5-fold higher plasma levels of 1 compared to oral administration of 1 itself. Subsequently, para-acetoxybenzyl-based prodrugs with additional ester promoiety(ies) on carboxylate(s) were examined for their ability to deliver 1 to plasma. Isopropyloxycarbonyloxymethyl (POC) ester 30 was the only prodrug that achieved substantial plasma levels of 1. In vitro metabolite identification studies confirmed stability of the ethyl ester of benzoate while the POC group was rapidly hydrolyzed. At oral daily dose-equivalent of 3 mg/kg, 12 exhibited analgesic efficacy comparable to dose of 10 mg/kg of 1 in the rat chronic constrictive injury model of neuropathic pain.
• NOVEL PRODRUG COMPOSITIONS AND UTILITY OF HYDROXAMATE-BASED GCPII INHIBITORS
  申请人：The Johns Hopkins University

  公开号：US20190352255A1

  公开（公告）日：2019-11-21

  Prodrugs of hydroxamate-based GCPII inhibitors and methods of their use for treating a disease or condition are disclosed.
• PRODRUGS OF HYDROXAMATE-BASED GCPII INHIBITORS
  申请人：The Johns Hopkins University

  公开号：US20210355079A1

  公开（公告）日：2021-11-18

  Prodrugs of hydroxamate-based GCPII inhibitors and methods of their use for treating a disease or condition are disclosed.
• [EN] PRODRUGS OF HYDROXAMATE-BASED GCPII INHIBITORS<br/>[FR] PROMÉDICAMENTS D'INHIBITEURS DE GCPII À BASE D'HYDROXAMATE
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2018094334A1

  公开（公告）日：2018-05-24

  Prodrugs of hydroxamate-based GCPII inhibitors and methods of their use for treating a disease or condition are disclosed.

  本发明揭示了羟肟基GCPII抑制剂的前药及其用于治疗疾病或病况的方法。