2-((allyloxy)methyl)-4-nitrophenol

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-((allyloxy)methyl)-4-nitrophenol
• 英文别名: 4-Nitro-2-(prop-2-enoxymethyl)phenol；4-nitro-2-(prop-2-enoxymethyl)phenol
• 化学式: C₁₀H₁₁NO₄
• 分子量: 209.202
• InChiKey: YBFYRFPWGKKSPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 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：

  2-((allyloxy)methyl)-4-nitrophenol 在 铁粉 、 potassium carbonate 、 氯化铵 作用下， 以 甲醇 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 22.0h， 生成
  参考文献：
  名称：

  [EN] JAK AND HDAC DUAL-INHIBITOR COMPOUNDS
  [FR] COMPOSÉS INHIBITEURS DOUBLES DE JAK ET DE HDAC

  摘要：

  本公开的描述提供了一种新颖的双重抑制化合物，专门针对JAK-STAT和HDAC途径，这两种不同的细胞途径对治疗各种疾病和障碍很有用。在某些方面，本文描述的化合物对细胞增殖性和炎症性疾病或障碍的治疗是有用的，例如移植物抗宿主病。在特定实施例中，本文描述的化合物抑制JAK2和HDAC6。

  公开号：

  WO2017196261A1
• 作为产物：
  描述：

  2-羟基-5-硝基苄醇 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 21.0h， 生成 2-((allyloxy)methyl)-4-nitrophenol
  参考文献：
  名称：

  Design and Synthesis of Janus Kinase 2 (JAK2) and Histone Deacetlyase (HDAC) Bispecific Inhibitors Based on Pacritinib and Evidence of Dual Pathway Inhibition in Hematological Cell Lines

  摘要：

  Blockage of more than one oncoptotein or pathway is now a standard approach in modem cancer therapy. Multiple inhibition is typically achieved with two or more drugs. Herein, we describe a pharmacophore Merging strategy combining the JAK2/FLT3 inhibitor pacritnib with the pan-HDAC inhibitor, vorinostat, to create bispecific single molecules with both JAK and HDAC targeted inhibition. A preferred ether hydroxamate, 51, inhibits JAK2 and HDAC6 with low nanomolar potency, is <100 nM potent against HDACs 2 and potent against HDACs 1, 8, and 11, and >50-, fold selective for JAK2 in a panel of 97 kinases. Broad cellular antiproliferative potency is supported by demonstration of JAK-STAT and HDAC pathway blockade in several hematological cell lines, inhibition of colony formation in HEL cells, and analysis of apoptosis. This study provides new tool compounds for further exploration of dual JAK-HDAC pathway inhibiton achieved with a single molecule.

  DOI：

  10.1021/acs.jmedchem.6b00157

文献信息

• [EN] JAK AND HDAC DUAL-INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DOUBLES DE JAK ET DE HDAC
  申请人：NAT UNIV SINGAPORE

  公开号：WO2017196261A1

  公开（公告）日：2017-11-16

  The present disclosure described provides novel dual inhibition compounds that specifically target the JAK-STAT and HDAC pathways, two distinct cellular pathways that are useful in the treatment of various diseases and disorders. In certain aspects, the compounds described herein are useful in the treatment of cellular proliferative and inflammatory diseases or disorders, such as graft vs. host disease. In particular embodiments, the compounds described herein inhibit JAK2 and HDAC6.

  本公开的描述提供了一种新颖的双重抑制化合物，专门针对JAK-STAT和HDAC途径，这两种不同的细胞途径对治疗各种疾病和障碍很有用。在某些方面，本文描述的化合物对细胞增殖性和炎症性疾病或障碍的治疗是有用的，例如移植物抗宿主病。在特定实施例中，本文描述的化合物抑制JAK2和HDAC6。
• New Ugi-Smiles-Metathesis Strategy toward the Synthesis of Pyrimido Azepines
  作者：Laurent El Kaïm、Laurence Grimaud、Julie Oble

  DOI：10.1021/jo070706c

  日期：2007.7.1

  A new strategy involving Ugi-Smiles coupling followed by ring-closure metathesis is described herein for the preparation of pyrimidine-fused heterocyclic scaffolds. The scope of this sequence is presented in relation with the heteroatom effect observed in the Ugi-Smiles coupling.
• Design and Synthesis of Janus Kinase 2 (JAK2) and Histone Deacetlyase (HDAC) Bispecific Inhibitors Based on Pacritinib and Evidence of Dual Pathway Inhibition in Hematological Cell Lines
  作者：Eugene Guorong Yang、Nurulhuda Mustafa、Eng Chong Tan、Anders Poulsen、Pondy Murugappan Ramanujulu、Wee Joo Chng、Jeffrey J. Y. Yen、Brian W. Dymock

  DOI：10.1021/acs.jmedchem.6b00157

  日期：2016.9.22

  Blockage of more than one oncoptotein or pathway is now a standard approach in modem cancer therapy. Multiple inhibition is typically achieved with two or more drugs. Herein, we describe a pharmacophore Merging strategy combining the JAK2/FLT3 inhibitor pacritnib with the pan-HDAC inhibitor, vorinostat, to create bispecific single molecules with both JAK and HDAC targeted inhibition. A preferred ether hydroxamate, 51, inhibits JAK2 and HDAC6 with low nanomolar potency, is <100 nM potent against HDACs 2 and potent against HDACs 1, 8, and 11, and >50-, fold selective for JAK2 in a panel of 97 kinases. Broad cellular antiproliferative potency is supported by demonstration of JAK-STAT and HDAC pathway blockade in several hematological cell lines, inhibition of colony formation in HEL cells, and analysis of apoptosis. This study provides new tool compounds for further exploration of dual JAK-HDAC pathway inhibiton achieved with a single molecule.