trans-4-[(2-amino-5-methoxybenzoylamino)methyl]cyclohexanecarboxylic acid methyl ester

• 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: trans-4-[(2-amino-5-methoxybenzoylamino)methyl]cyclohexanecarboxylic acid methyl ester
• 英文别名: trans-methyl 4-((2-amino-5-methoxybenzamido)methyl)cyclohexanecarboxylate；Methyl 4-[[(2-amino-5-methoxybenzoyl)amino]methyl]cyclohexane-1-carboxylate；methyl 4-[[(2-amino-5-methoxybenzoyl)amino]methyl]cyclohexane-1-carboxylate
• 化学式: C₁₇H₂₄N₂O₄
• 分子量: 320.389
• InChiKey: CYWHAJFWQPNPRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  trans-4-[(2-amino-5-methoxybenzoylamino)methyl]cyclohexanecarboxylic acid methyl ester 在 N,N'-羰基二咪唑 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Process Development and Scale-Up for the Preparation of the 1-Methyl-quinazoline-2,4-dione Wnt Inhibitor SEN461

  摘要：

  A practical and scalable route to the Wnt inhibitor SEN461 1 is described herein. The optimized route consists of nine chemical steps. The intermediates are solids and were isolated by filtrations. Critical reactions steps in the medicinal chemistry route were modified for an initial scale-up process, and as a result, we developed a synthetic procedure for the preparation of multihundred gram quantities of the final product. A further process development for the phase 1 clinical batch campaign is reported.

  DOI：

  10.1021/op400145w
• 作为产物：
  描述：

  5-甲氧基-2-硝基苯甲酸 在 甲醇 、 palladium on activated charcoal 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 生成 trans-4-[(2-amino-5-methoxybenzoylamino)methyl]cyclohexanecarboxylic acid methyl ester
  参考文献：
  名称：

  [EN] QUINAZOLINEDIONES AS TANKYRASE INHIBITORS
  [FR] INHIBITEURS DE TANKYRASE DE TYPE QUINAZOLINEDIONES

  摘要：

  公开号：

  WO2013177349A3

文献信息

• [EN] QUINAZOLINEDIONES AS TANKYRASE INHIBITORS<br/>[FR] INHIBITEURS DE TANKYRASE DE TYPE QUINAZOLINEDIONES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2013177349A3

  公开（公告）日：2014-01-16
• Structure–activity relationship and properties optimization of a series of Quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway
  作者：Arianna Nencini、Carmela Pratelli、Joanna M. Quinn、Massimiliano Salerno、Patrizia Tunici、Alessandra De Robertis、Silvia Valensin、Federica Mennillo、Marco Rossi、Annette Bakker、Tiziana Benicchi、Federico Cappelli、Elisa Turlizzi、Martina Nibbio、Nicola P. Caradonna、Ugo Zanelli、Matteo Andreini、Matteo Magnani、Maurizio Varrone

  DOI：10.1016/j.ejmech.2015.03.055

  日期：2015.5

  Wnt signaling pathway plays a critical role in numerous cellular processes, including tumor initiation, proliferation, invasion/infiltration, metastasis formation and resistance to chemotherapy. In a drug discovery project aimed at the identification of inhibitors of the canonical Wnt pathway, we selected a series of quinazoline 2,4-diones as starting point for the therapeutic treatment of glioblastoma multiforme. Despite of poor physico-chemical properties of hit compound I, our medicinal chemistry effort allowed the discovery and characterization of lead compound 33 (SEN461), with improved ADME profile, good bioavailability and active in vitro and in vivo in glioblastoma, gastric and sarcoma tumors. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Process Development and Scale-Up for the Preparation of the 1-Methyl-quinazoline-2,4-dione Wnt Inhibitor SEN461
  作者：Matteo Betti、Eva Genesio、Alessandro Panico、Salvatore Sanna Coccone、Paul Wiedenau

  DOI：10.1021/op400145w

  日期：2013.8.16

  A practical and scalable route to the Wnt inhibitor SEN461 1 is described herein. The optimized route consists of nine chemical steps. The intermediates are solids and were isolated by filtrations. Critical reactions steps in the medicinal chemistry route were modified for an initial scale-up process, and as a result, we developed a synthetic procedure for the preparation of multihundred gram quantities of the final product. A further process development for the phase 1 clinical batch campaign is reported.