4-(naphthalen-2-yloxy)-3-(trifluoromethyl)aniline | 71311-90-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(naphthalen-2-yloxy)-3-(trifluoromethyl)aniline
• 英文别名: 4-(2-naphthyloxy)-3-trifluoromethyl-aniline；3-trifluoromethyl-4-(2-naphthyloxy)aniline；4-Naphthoxy-3-trifluormethylphenylamin；4-(2-Naphthyloxy)-3-(trifluoromethyl)aniline；4-naphthalen-2-yloxy-3-(trifluoromethyl)aniline
• CAS: 71311-90-5
• 化学式: C₁₇H₁₂F₃NO
• 分子量: 303.284
• InChiKey: AVRAIKCZBQKOFX-UHFFFAOYSA-N

物化性质

• 沸点：
  407.8±45.0 °C(Predicted)
• 密度：
  1.319±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  4-(naphthalen-2-yloxy)-3-(trifluoromethyl)aniline 、 3,5-二氯-2-羟基苯甲酰氯 在 苯酐 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 3,5-dichloro-2-hydroxy-N-(4-(naphthalen-2-yloxy)-3-(trifluoromethyl)phenyl)benzamide
  参考文献：
  名称：

  Discovery and Structure–Activity Relationships of Modified Salicylanilides as Cell Permeable Inhibitors of Poly(ADP-ribose) Glycohydrolase (PARG)

  摘要：

  The metabolism of poly(ADP-ribose) (PAR) in response to DNA strand breaks, which involves the concerted activities of poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolase (PARG), modulates cell recovery or cell death depending upon the level of DNA damage. While PARP inhibitors show high promise in clinical trials because of their low toxicity and selectivity for BRCA related cancers, evaluation of the therapeutic potential of PARG is limited by the lack of well-validated cell permeable inhibitors. In this study, target-related affinity profiling (TRAP), an alternative to high-throughput screening, was used to identify a number of druglike compounds from several chemical classes that demonstrated PARG inhibition in the low-micromolar range. A number of analogues of one of the most active chemotypes were synthesized to explore the structure activity relationship (SAR) for that series. This led to the discovery of a putative pharmacophore for PARG inhibition that contains a modified salicylanilide structure. Interestingly, these compounds also inhibit PARP-1, indicating strong homology in the active sites of PARG and PARP-1 and raising a new challenge for development of PARG specific inhibitors. The cellular activity of a lead inhibitor was demonstrated by the inhibition of both PARP and PARG activity in squamous cell carcinoma cells, although preferential inhibition of PARG relative to PARP was observed. The ability of inhibitors to modulate PAR metabolism via simultaneous effects on PARPs and PARG may represent a new approach for therapeutic development.

  DOI：

  10.1021/jm200325s
• 作为产物：
  描述：

  2-氟-5-硝基三氟甲苯 在 铁粉 、 potassium carbonate 、 溶剂黄146 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 4-(naphthalen-2-yloxy)-3-(trifluoromethyl)aniline
  参考文献：
  名称：

  脂蛋白相关的磷脂酶A2的新型，有效和口服生物利用抑制剂的结构指导的发现。

  摘要：

  脂蛋白相关的磷脂酶A2（Lp-PLA2）是动脉粥样硬化，阿尔茨海默氏病和糖尿病性黄斑水肿的有希望的治疗靶标。在这里，我们报告鉴定衍生自相对较弱的片段的新型磺酰胺支架Lp-PLA2抑制剂。在该片段上进行相似搜索，然后进行分子对接，导致发现了一种微摩尔抑制剂，其效价提高了300倍。随后，通过应用结构指导的设计策略，成功实现了从头至尾的优化，并获得了许多具有单位数纳摩尔效价的Lp-PLA2抑制剂。在初步评估了体内和体外的药物相似性后，将化合物37该同类抑制剂系列在雄性Sprague-Dawley大鼠中具有良好的抑制活性和良好的口服生物利用度，从而脱颖而出，为进一步开发提供了良好的候选者。因此，本研究清楚地证明了在有效的铅发现项目中整合使用片段筛选，晶体结构确定，虚拟筛选和药物化学的功能和优势，为基于结构的药物设计提供了一个很好的例子。

  DOI：

  10.1021/acs.jmedchem.7b01530

文献信息

• Herbicidal N-phenyl-N-methylurea derivatives
  申请人：Sumitomo Chemical Company, Limited

  公开号：US04280835A1

  公开（公告）日：1981-07-28

  Novel N'-4-(2-naphthyloxy)phenyl-N-methylurea derivatives of the formula: ##STR1## wherein X is a hydrogen atom, a halogen atom or a trifluoromethyl group and R is a methyl or methoxy group having a herbicidal activity, particularly effective in exterminating weeds in the cultivation of soybean and gramineous crops such as wheat and barley, and/or having a fungicidal activity especially effective in controlling the rust of wheat and barley.

  这是一种化合物，化学式为：##STR1## 其中X为氢原子、卤素原子或三氟甲基基团，R为甲基或甲氧基基团，具有除草活性，特别是在大豆和小麦、大麦等禾本科作物的栽培中，具有高效的除草作用，并且具有杀菌活性，特别是在控制小麦和大麦锈病方面具有高效的作用。
• N-Phenyl-N-methylurea derivatives
  申请人：Sumitomo Chemical Company, Limited

  公开号：US04399072A1

  公开（公告）日：1983-08-16

  Novel N'-4-(2-naphthyloxy)phenyl-N-methylurea derivatives of the formula: ##STR1## wherein X is a hydrogen atom, a halogen atom or a trifluoromethyl group and R is a methyl or methoxy group having a herbicidal activity, particularly effective in exterminating weeds in the cultivation of soybean and gramineous crops such as wheat and barley, and/or having a fungicidal activity especially effective in controlling the rust of wheat and barley.

  该分子式为：##STR1## 其中X为氢原子、卤素原子或三氟甲基基团，R为甲基或甲氧基基团，具有除草活性，特别是在大豆和禾本科作物如小麦和大麦的种植中，具有很高的除草效果，同时也具有杀菌活性，特别是在控制小麦和大麦的锈病方面具有很高的效果。
• US4280835A
  申请人：——

  公开号：US4280835A

  公开（公告）日：1981-07-28
• US4399072A
  申请人：——

  公开号：US4399072A

  公开（公告）日：1983-08-16
• Discovery and Structure–Activity Relationships of Modified Salicylanilides as Cell Permeable Inhibitors of Poly(ADP-ribose) Glycohydrolase (PARG)
  作者：Jamin D. Steffen、Donna L. Coyle、Komath Damodaran、Paul Beroza、Myron K. Jacobson

  DOI：10.1021/jm200325s

  日期：2011.8.11

  The metabolism of poly(ADP-ribose) (PAR) in response to DNA strand breaks, which involves the concerted activities of poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolase (PARG), modulates cell recovery or cell death depending upon the level of DNA damage. While PARP inhibitors show high promise in clinical trials because of their low toxicity and selectivity for BRCA related cancers, evaluation of the therapeutic potential of PARG is limited by the lack of well-validated cell permeable inhibitors. In this study, target-related affinity profiling (TRAP), an alternative to high-throughput screening, was used to identify a number of druglike compounds from several chemical classes that demonstrated PARG inhibition in the low-micromolar range. A number of analogues of one of the most active chemotypes were synthesized to explore the structure activity relationship (SAR) for that series. This led to the discovery of a putative pharmacophore for PARG inhibition that contains a modified salicylanilide structure. Interestingly, these compounds also inhibit PARP-1, indicating strong homology in the active sites of PARG and PARP-1 and raising a new challenge for development of PARG specific inhibitors. The cellular activity of a lead inhibitor was demonstrated by the inhibition of both PARP and PARG activity in squamous cell carcinoma cells, although preferential inhibition of PARG relative to PARP was observed. The ability of inhibitors to modulate PAR metabolism via simultaneous effects on PARPs and PARG may represent a new approach for therapeutic development.