methyl 1-(1-adamantyl)-3-(4-aminosalicylate)urea | 1068522-74-6

• 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 1-(1-adamantyl)-3-(4-aminosalicylate)urea
• 英文别名: methyl 4-(3-adamantan-1-ylureido)-2-hydroxybenzoate；methyl 4-(3-(1-adamantyl)ureido)-2-hydroxybenzoate；Methyl 4-(1-adamantylcarbamoylamino)-2-hydroxy-benzoate；methyl 4-(1-adamantylcarbamoylamino)-2-hydroxybenzoate
• CAS: 1068522-74-6
• 化学式: C₁₉H₂₄N₂O₄
• 分子量: 344.411
• InChiKey: PXJSHQUWAKRZPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1-(1-adamantyl)-3-(4-aminosalicylate)urea 在 sodium hydroxide 、 水 作用下， 以 甲醇 为溶剂， 生成 4-(3-adamantan-1-ylureido)-2-hydroxybenzoic acid
  参考文献：
  名称：

  Salicylate–urea-based soluble epoxide hydrolase inhibitors with high metabolic and chemical stabilities

  摘要：

  We investigated N-adamantyl-N'-phenyl urea derivatives as simple sEH inhibitors. Salicylate ester derivatives have high inhibitory activities against human sEH, while the free benzoic acids are less active. The methyl salicylate derivative is a potent sEH inhibitor, which also has high metabolic and chemical stabilities; suggesting that such inhibitors are potential lead molecule for bioactive compounds acting in vivo. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.01.069
• 作为产物：
  描述：

  methyl 2-hydroxy-4-isocyanatobenzoate 、 金刚烷胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以41%的产率得到methyl 1-(1-adamantyl)-3-(4-aminosalicylate)urea
  参考文献：
  名称：

  The structure–activity relationship of urea derivatives as anti-tuberculosis agents

  摘要：

  The treatment of tuberculosis is becoming more difficult due to the ever increasing prevalence of drug resistance. Thus, it is imperative that novel anti-tuberculosis agents, with unique mechanisms of action, be discovered and developed. The direct anti-tubercular testing of a small compound library led to discovery of adamantyl urea hit compound 1. In this study, the hit was followed up through the synthesis of an optimization library. This library was generated by systematically replacing each section of the molecule with a similar moiety until a clear structure-activity relationship was obtained with respect to antitubercular activity. The best compounds in this series contained a 1-adamantyl-3-phenyl urea core and had potent activity against Mycobacterium tuberculosis plus an acceptable therapeutic index. It was noted that the compounds identified and the pharmacophore developed is consistent with inhibitors of epoxide hydrolase family of enzymes. Consequently, the compounds were tested for inhibition of representative epoxide hydrolases: M. tuberculosis EphB and EphE; and human soluble epoxide hydrolase. Many of the optimized inhibitors showed both potent EphB and EphE inhibition suggesting the antitubercular activity is through inhibition of multiple epoxide hydrolase enzymes. The inhibitors also showed potent inhibition of humans soluble epoxide hydrolase, but limited cytotoxicity suggesting that future studies must be towards increasing the selectivity of epoxide hydrolase inhibition towards the M. tuberculosis enzymes. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.034

文献信息

• Chemical Probes to Identify Anti-Mycobacterial MmpL3 Inhibitors
  申请人：Creighton University

  公开号：US20200331897A1

  公开（公告）日：2020-10-22

  The present application provides detectable compounds useful for identifying compounds that bind (e.g., inhibit) MmpL3. Methods of identifying compounds that bind and/or inhibit MmpL3 are also provided.

  本申请提供了可检测的化合物，可用于识别与MmpL3结合（例如抑制）的化合物。还提供了识别与/或抑制MmpL3结合的方法。
• Compounds and methods for inhibiting Cif virulence factor
  申请人：Trustees of Dartmouth College

  公开号：US10322118B2

  公开（公告）日：2019-06-18

  The present invention provides a screening assay for identifying inhibitors of Pseudomonas aeruginosa CFTR Inhibitory Factor as well as compositions and methods for ameliorating or treating a respiratory disease such as cystic fibrosis or secondary infection thereof.

  本发明提供了一种用于鉴定铜绿假单胞菌 CFTR 抑制因子抑制剂的筛选试验，以及用于改善或治疗呼吸道疾病（如囊性纤维化）或继发感染的组合物和方法。
• COMPOUNDS AND METHODS FOR INHIBITING CIF VIRULENCE FACTOR
  申请人：Trustees of Dartmouth College

  公开号：US20150045389A1

  公开（公告）日：2015-02-12

  The present invention is a screening assay for identifying inhibitors of Pseudomonas aeruginosa CFTR Inhibitory Factor as well as compounds identified by the screening assay for use in compositions and methods for ameliorating or treating a respiratory disease such as cystic fibrosis or secondary infection thereof.
• [EN] COMPOUNDS AND METHODS FOR INHIBITING CIF VIRULENCE FACTOR<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR L'INHIBITION DU FACTEUR DE VIRULENCE CIF
  申请人：DARTMOUTH COLLEGE

  公开号：WO2013155047A2

  公开（公告）日：2013-10-17

  The present invention is a screening assay for identifying inhibitors of Pseudomonas aeruginosa CFTR Inhibitory Factor as well as compounds identified by the screening assay for use in compositions and methods for ameliorating or treating a respiratory disease such as cystic fibrosis or secondary infection thereof.
• The structure–activity relationship of urea derivatives as anti-tuberculosis agents
  作者：Joshua R. Brown、Elton J. North、Julian G. Hurdle、Christophe Morisseau、Jerrod S. Scarborough、Dianqing Sun、Jana Korduláková、Michael S. Scherman、Victoria Jones、Anna Grzegorzewicz、Rebecca M. Crew、Mary Jackson、Michael R. McNeil、Richard E. Lee

  DOI：10.1016/j.bmc.2011.07.034

  日期：2011.9

  The treatment of tuberculosis is becoming more difficult due to the ever increasing prevalence of drug resistance. Thus, it is imperative that novel anti-tuberculosis agents, with unique mechanisms of action, be discovered and developed. The direct anti-tubercular testing of a small compound library led to discovery of adamantyl urea hit compound 1. In this study, the hit was followed up through the synthesis of an optimization library. This library was generated by systematically replacing each section of the molecule with a similar moiety until a clear structure-activity relationship was obtained with respect to antitubercular activity. The best compounds in this series contained a 1-adamantyl-3-phenyl urea core and had potent activity against Mycobacterium tuberculosis plus an acceptable therapeutic index. It was noted that the compounds identified and the pharmacophore developed is consistent with inhibitors of epoxide hydrolase family of enzymes. Consequently, the compounds were tested for inhibition of representative epoxide hydrolases: M. tuberculosis EphB and EphE; and human soluble epoxide hydrolase. Many of the optimized inhibitors showed both potent EphB and EphE inhibition suggesting the antitubercular activity is through inhibition of multiple epoxide hydrolase enzymes. The inhibitors also showed potent inhibition of humans soluble epoxide hydrolase, but limited cytotoxicity suggesting that future studies must be towards increasing the selectivity of epoxide hydrolase inhibition towards the M. tuberculosis enzymes. (C) 2011 Elsevier Ltd. All rights reserved.