methyl 2-hydroxy-5-[2-(4-trifluoromethylphenyl)ethylamino]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: methyl 2-hydroxy-5-[2-(4-trifluoromethylphenyl)ethylamino]benzoate
• 英文别名: Methyl 2-Hydroxy-5-[[4-(trifluoromethyl)phenethyl]amino)benzoate；methyl 2-hydroxy-5-[2-[4-(trifluoromethyl)phenyl]ethylamino]benzoate
• 化学式: C₁₇H₁₆F₃NO₃
• 分子量: 339.314
• InChiKey: XJTMALBKPQBKIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 2-hydroxy-5-[2-(4-trifluoromethylphenyl)ethylamino]benzoate 在 硫酸 、 水 、 溶剂黄146 、 氨 作用下， 以 乙醇 、 水 为溶剂， 反应 27.0h， 生成 2-羟基-5-[2-[4-(三氟甲基)苯基]乙胺基]苯甲酸
  参考文献：
  名称：

  [EN] MANUFACTURING METHOD OF 2-HYDROXY-5-PHENYLALKYLAMINOBENZOIC ACID DERIVATIVES AND THEIR SALTS
  [FR] PROCÉDÉ DE PRODUCTION DE DÉRIVÉS D'ACIDE 2-HYDROXY-5-PHÉNYLALKYLAMINOBENZOÏQUE ET LEUR SELS

  摘要：

  公开号：

  WO2009064084A3
• 作为产物：
  描述：

  methanesulfonic acid 2-(4-(trifluoromethyl)phenyl)ethyl ester 、 5-氨基水杨酸甲酯 在 三乙胺 作用下， 以 甲苯 为溶剂， 以58.4%的产率得到methyl 2-hydroxy-5-[2-(4-trifluoromethylphenyl)ethylamino]benzoate
  参考文献：
  名称：

  [EN] MANUFACTURING METHOD OF 2-HYDROXY-5-PHENYLALKYLAMINOBENZOIC ACID DERIVATIVES AND THEIR SALTS
  [FR] PROCÉDÉ DE PRODUCTION DE DÉRIVÉS D'ACIDE 2-HYDROXY-5-PHÉNYLALKYLAMINOBENZOÏQUE ET LEUR SELS

  摘要：

  公开号：

  WO2009064084A3

文献信息

• MANUFACTURING METHOD OF 2-HYDROXY-5-PHENYLALKYLAMINOBENZOIC ACID DERIVATIVES AND THEIR SALTS
  申请人：Gwag Byoung Joo

  公开号：US20110028757A1

  公开（公告）日：2011-02-03

  The present invention provides an efficient method for mass-producing 2-hydroxy-5-(substituted)phenylalkylaminobenzoic acid derivative represented by the specific Chemical formula or its salt, particularly 2-hydroxy-5-[2-(4-trifluoromethylphenyl)ethylamino] benzoic acid or its salt.

  本发明提供了一种高效的方法，用于大规模生产特定化学式或其盐所代表的2-羟基-5-(取代)苯基烷基氨基苯甲酸衍生物，特别是2-羟基-5-[2-(4-三氟甲基苯基)乙基]氨基苯甲酸或其盐。
• [EN] METHOD FOR PREPARING 2-HYDROXY-5-[2-(4-(TRIFLUOROMETHYLPHENYL)ETHYLAMINO)]BENZOIC ACID<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ACIDE 2-HYDROXY-5-[2-(4-(TRIFLUOROMÉTHYLPHÉNYL)ÉTHYLAMINO)]BENZOÏQUE<br/>[ZH] 2-羟基-5-[2-(4-(三氟甲基苯基)乙基氨基)]苯甲酸的制备方法
  申请人：[en]GNT PHARMA CO., LTD.;[zh]吉恩特药业株式会社

  公开号：WO2022121853A1

  公开（公告）日：2022-06-16

  本发明属于药物合成方法技术领域，涉及2-羟基-5-[2-(4-(三氟甲基苯基)乙基氨基)]苯甲酸的制备方法。该方法包括保护、缩合和水解等步骤，通过筛选针对起始原料2-(4-三氟甲基)苯乙醇的羟基保护试剂，并配合其他工艺参数的优化，有效控制了目标产物中间位异构体杂质及二取代杂质的含量，使产品质量得到显著改善，同时反应收率也大幅提高，改进后的产品质量可以满足制剂研究的相关要求。
• Concurrent blockade of free radical and microsomal prostaglandin E synthase-1-mediated PGE2 production improves safety and efficacy in a mouse model of amyotrophic lateral sclerosis
  作者：Jin Hee Shin、Young Ae Lee、Jae Keun Lee、Yong Beom Lee、Woong Cho、Doo Soon Im、Jin Hwan Lee、Bok Sun Yun、Joe E. Springer、Byoung Joo Gwag

  DOI：10.1111/j.1471-4159.2012.07771.x

  日期：2012.9

  J. Neurochem. (2012) 122, 952–961.AbstractWhile free radicals and inflammation constitute major routes of neuronal injury occurring in amyotrophic lateral sclerosis (ALS), neither antioxidants nor non‐steroidal anti‐inflammatory drugs have shown significant efficacy in human clinical trials. We examined the possibility that concurrent blockade of free radicals and prostaglandin E2 (PGE2)‐mediated inflammation might constitute a safe and effective therapeutic approach to ALS. We have developed 2‐hydroxy‐5‐[2‐(4‐trifluoromethylphenyl)‐ethylaminobenzoic acid] (AAD‐2004) as a derivative of aspirin. AAD‐2004 completely removed free radicals at 50 nM as a potent spin‐trapping molecule and inhibited microsomal PGE2 synthase‐1 (mPGES‐1) activity in response to both lipopolysaccharide‐treated BV2 cell with IC50 of 230 nM and recombinant human mPGES‐1 protein with IC50 of 249 nM in vitro. In superoxide dismutase 1G93A transgenic mouse model of ALS, AAD‐2004 blocked free radical production, PGE2 formation, and microglial activation in the spinal cords. As a consequence, AAD‐2004 reduced autophagosome formation, axonopathy, and motor neuron degeneration, improving motor function and increasing life span. In these assays, AAD‐2004 was superior to riluzole or ibuprofen. Gastric bleeding was not induced by AAD‐2004 even at a dose 400‐fold higher than that required to obtain maximal therapeutic efficacy in superoxide dismutase 1G93A. Targeting both mPGES‐1‐mediated PGE2 and free radicals may be a promising approach to reduce neurodegeneration in ALS and possibly other neurodegenerative diseases.