[4-[(2-nitrophenyl)methoxy]phenyl]methanol | 191851-56-6

• 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: [4-[(2-nitrophenyl)methoxy]phenyl]methanol
• 英文别名: para-(ortho-nitrobenzyloxy)-hydroxybenzyl alcohol
• CAS: 191851-56-6
• 化学式: C₁₄H₁₃NO₄
• 分子量: 259.262
• InChiKey: MUOATOYDMDHIPU-UHFFFAOYSA-N

物化性质

• 沸点：
  439.1±30.0 °C(Predicted)
• 密度：
  1.297±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 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-[(2-nitrophenyl)methoxy]phenyl]methanol 在 4-二甲氨基吡啶 、 platinum(IV) oxide 、 氯化亚砜 、 偶氮二甲酸二异丙酯 、 氢气 、 N,N-二甲基甲酰胺 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 甲苯 、 乙腈 为溶剂， 75.0 ℃ 、101.33 kPa 条件下， 反应 14.25h， 生成 N-[2-[[4-(guanidinomethyl)phenoxy]methyl]phenyl]-4-methyl-thieno[3,2-b]pyrrole-5-carboxamide trifluoroacetic acid salt
  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：

  2-硝基苄溴 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 3.0h， 生成 [4-[(2-nitrophenyl)methoxy]phenyl]methanol
  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

文献信息

• HIV protease inhibitors
  申请人：Wong Chi-Huey

  公开号：US06900238B1

  公开（公告）日：2005-05-31

  Combinatorial libraries of HIV and FIV protease inhibitors are characterized by α-keto amide or hydroxyethylamine core structures flanked by on one side by substituted pyrrolidines, piperidines, or azasugars and on the other side by phenylalanine, tyrosine, or substituted tyrosines. The libraries are synthesized via a one step coupling reaction. Highly efficacious drug candidates are identified by screening the libraries for binding and inhibitory activity against both HIV and FIV protease. Drug candidates displaying clinically useful activity against both HIV and FIV protease are identified as being potentially resistive against a loss of inhibitory activity due to development of resistant strains of HIV.

  HIV和FIV蛋白酶抑制剂的组合库以α-酮酰胺或羟乙基胺核心结构为特征，一侧为取代吡咯烷、哌啶或氮代糖，另一侧为苯丙氨酸、酪氨酸或取代酪氨酸。这些库是通过一步偶联反应合成的。通过筛选这些库，识别出对HIV和FIV蛋白酶的结合和抑制活性高效的药物候选化合物。对HIV和FIV蛋白酶都显示出临床有用活性的药物候选化合物被确定为潜在对抗由于HIV耐药株的发展而导致的抑制活性丧失。
• Photoactivated Hydrogen Sulfide Donor with a Near-Infrared Fluorescence Report System for Accelerated Chronic Wound Healing
  作者：Fang Yuan、Xiaomeng He、Yurong Lu、Lulu Ning、Xinyue Zhao、Suya Zhang、Feng Guan、Yuan Guo、Jianjian Zhang

  DOI：10.1021/acs.analchem.3c00230

  日期：2023.5.2
• 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.