4-(4-nitrobenzyloxy)phenol | 512848-04-3

• 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: 4-(4-nitrobenzyloxy)phenol
• 英文别名: 4-[(4-nitrophenyl)methoxy]phenol
• CAS: 512848-04-3
• 化学式: C₁₃H₁₁NO₄
• mdl: MFCD11540333
• 分子量: 245.235
• InChiKey: OOWZNXYWXVXDSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-nitrobenzyloxy)phenol 在 platinum(IV) oxide 、 偶氮二甲酸二异丙酯 、 氢气 、 sodium cyanoborohydride 、 溶剂黄146 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 70.0 ℃ 、101.33 kPa 条件下， 生成 4-[[4-[(1-methyl-4-piperidyl)oxy]phenoxy]methyl]aniline
  参考文献：
  名称：

  Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 2: Structure-Based Drug Design and Structure–Activity Relationship

  摘要：

  The balance of methylation levels at histone H3 lysine 4 (H3K4) is regulated by KDM1A (LSD1). KDM1A is overexpressed in several tumor types, thus representing an emerging target for the development of novel cancer therapeutics. We have previously described (Part 1, DOI 10.1021.acs.jmedchem.6b01018) the identification of thieno[3,2-b]pyrrole-5-carboxamides as novel reversible inhibitors of KDM1A, whose preliminary exploration resulted in compound 2 with biochemical IC50 = 160 nM. We now report the structure-guided optimization of this chemical series based on multiple ligand/KDM1A-CoRest cocrystal structures, which led to several extremely potent inhibitors. In particular, compounds 46, 49, and 50 showed single-digit nanomolar IC50 values for in vitro inhibition of KDM1A, with high selectivity in secondary assays. In THP-1 cells, these compounds transcriptionally affected the expression of genes regulated by KDM1A such as CD14, CD11b, and CD86. Moreover, 49 and SO showed a remarkable anticlonogenic cell growth effect on MLL-AF9 human leukemia cells.

  DOI：

  10.1021/acs.jmedchem.6b01019
• 作为产物：
  描述：

  对苯二酚 、 对硝基溴化苄 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以37%的产率得到4-(4-nitrobenzyloxy)phenol
  参考文献：
  名称：

  由苯酚直接合成苯胺和亚硝基苯†

  摘要：

  已经使用ipso-氧化性芳族取代（i S O Ar）方法开发了一种从苯酚一锅合成苯胺和亚硝基苯的方法。在温和且不含金属的条件下，可以以高收率获得产品。还研究了离去基团对通过混合的醌酮单缩酮进行的反应的影响，并建立了预测模型。

  DOI：

  10.1039/c6ob00073h

文献信息

• Direct synthesis of anilines and nitrosobenzenes from phenols
  作者：A. H. St. Amant、C. P. Frazier、B. Newmeyer、K. R. Fruehauf、J. Read de Alaniz

  DOI：10.1039/c6ob00073h

  日期：——

  A one-pot synthesis of anilines and nitrosobenzenes from phenols has been developed using an ipso-oxidative aromatic substitution (iSOAr) process. The products are obtained in good yields under mild and metal-free conditions. The leaving group effect on reactions that proceed through mixed quionone monoketals has also been investigated and a predictive model has been established.

  已经使用ipso-氧化性芳族取代（i S O Ar）方法开发了一种从苯酚一锅合成苯胺和亚硝基苯的方法。在温和且不含金属的条件下，可以以高收率获得产品。还研究了离去基团对通过混合的醌酮单缩酮进行的反应的影响，并建立了预测模型。
• US5538940A
  申请人：——

  公开号：US5538940A

  公开（公告）日：1996-07-23
• US5573999A
  申请人：——

  公开号：US5573999A

  公开（公告）日：1996-11-12
• Thieno[3,2-<i>b</i>]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 2: Structure-Based Drug Design and Structure–Activity Relationship
  作者：Paola Vianello、Luca Sartori、Federica Amigoni、Anna Cappa、Giovanni Fagá、Raimondo Fattori、Elena Legnaghi、Giuseppe Ciossani、Andrea Mattevi、Giuseppe Meroni、Loris Moretti、Valentina Cecatiello、Sebastiano Pasqualato、Alessia Romussi、Florian Thaler、Paolo Trifiró、Manuela Villa、Oronza A. Botrugno、Paola Dessanti、Saverio Minucci、Stefania Vultaggio、Elisa Zagarrí、Mario Varasi、Ciro Mercurio

  DOI：10.1021/acs.jmedchem.6b01019

  日期：2017.3.9

  The balance of methylation levels at histone H3 lysine 4 (H3K4) is regulated by KDM1A (LSD1). KDM1A is overexpressed in several tumor types, thus representing an emerging target for the development of novel cancer therapeutics. We have previously described (Part 1, DOI 10.1021.acs.jmedchem.6b01018) the identification of thieno[3,2-b]pyrrole-5-carboxamides as novel reversible inhibitors of KDM1A, whose preliminary exploration resulted in compound 2 with biochemical IC50 = 160 nM. We now report the structure-guided optimization of this chemical series based on multiple ligand/KDM1A-CoRest cocrystal structures, which led to several extremely potent inhibitors. In particular, compounds 46, 49, and 50 showed single-digit nanomolar IC50 values for in vitro inhibition of KDM1A, with high selectivity in secondary assays. In THP-1 cells, these compounds transcriptionally affected the expression of genes regulated by KDM1A such as CD14, CD11b, and CD86. Moreover, 49 and SO showed a remarkable anticlonogenic cell growth effect on MLL-AF9 human leukemia cells.