N-ethyl-3-hydroxy-4-nitrobenzamide | 912838-90-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: N-ethyl-3-hydroxy-4-nitrobenzamide
• CAS: 912838-90-5
• 化学式: C₉H₁₀N₂O₄
• mdl: MFCD23714702
• 分子量: 210.189
• InChiKey: YEVKOIYXOCRNQV-UHFFFAOYSA-N

物化性质

• 沸点：
  359.7±32.0 °C(Predicted)
• 密度：
  1.342±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  95.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-ethyl-3-hydroxy-4-nitrobenzamide 在 铁粉 、 溶剂黄146 作用下， 反应 2.0h， 生成 4-amino-N-ethyl-3-hydroxybenzamide
  参考文献：
  名称：

  Structure-based design and SAR development of novel selective polo-like kinase 1 inhibitors having the tetrahydropteridin scaffold

  摘要：

  Polo-like kinase 1 (Plk1) is a validated target for the treatment of cancer. In this report, by analyzing amino acid residue differences among the ATP-binding pockets of Plk1, P1k2 and Plk3, novel selective Plk1 inhibitors were designed based on BI 2536 and BI 6727, two Plk1 inhibitors in clinical studies for cancer treatments. The Plkl inhibitors reported herein have more potent inhibition against Plk1 and better isoform selectivity in the Plk family than these two lead compounds. In addition, by introducing a hydroxyl group, our compounds have significantly improved solubility and may target specific polar residues Arg57, Glu69 and Arg134 of Plk1. Moreover, most of our compounds exhibited antitumor activities in the nanomolar range against several cancer cell lines in the MTT assay. Through this structure-based design strategy and SAR study, a few promising selective Plk1 inhibitors having the tetrahy-dropteridin scaffold, for example, L34, were identified and could be for further anticancer research. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111769
• 作为产物：
  描述：

  3-羟基-4-硝基苯甲酸 、 乙胺 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 N-ethyl-3-hydroxy-4-nitrobenzamide
  参考文献：
  名称：

  Structure-based design and SAR development of novel selective polo-like kinase 1 inhibitors having the tetrahydropteridin scaffold

  摘要：

  Polo-like kinase 1 (Plk1) is a validated target for the treatment of cancer. In this report, by analyzing amino acid residue differences among the ATP-binding pockets of Plk1, P1k2 and Plk3, novel selective Plk1 inhibitors were designed based on BI 2536 and BI 6727, two Plk1 inhibitors in clinical studies for cancer treatments. The Plkl inhibitors reported herein have more potent inhibition against Plk1 and better isoform selectivity in the Plk family than these two lead compounds. In addition, by introducing a hydroxyl group, our compounds have significantly improved solubility and may target specific polar residues Arg57, Glu69 and Arg134 of Plk1. Moreover, most of our compounds exhibited antitumor activities in the nanomolar range against several cancer cell lines in the MTT assay. Through this structure-based design strategy and SAR study, a few promising selective Plk1 inhibitors having the tetrahy-dropteridin scaffold, for example, L34, were identified and could be for further anticancer research. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111769

文献信息

• Triazole Derivative and Use Thereof
  申请人：Kubo Keiji

  公开号：US20090105253A1

  公开（公告）日：2009-04-23

  The present invention relates to a thrombin receptor antagonist containing a compound represented by the formula (I) wherein R 1a , R 1b and R 2 are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted alkoxy, R 3 is a group represented by the formula —NHCOR 4 , —NHSO 2 R 5 , —NHCON(R 6a )(R 6b ), —NHCOOR 7 or —CONHR 8 wherein R 4 , R 5 , R 6a , R 6b , R 7 and R 8 are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like), ring A is monocyclic aromatic ring optionally further having substituent(s), R 1a and R 1b are optionally bonded to each other to form an optionally substituted nitrogen-containing non-aromatic heterocycle, or a salt thereof or a prodrug thereof. The thrombin receptor antagonist of the present invention has a thrombin receptor (particularly PAR-1) antagonistic action and is useful for the prophylaxis or treatment of PAR-1 mediated pathological condition or disease.

  本发明涉及一种含有式(I)所表示的化合物的凝血酶受体拮抗剂，其中R1a、R1b和R2分别是氢原子、可选取代的碳氢基团、可选取代的杂环基团或可选取代的烷氧基，R3是由式—NHCOR4、—NHSO2R5、—NHCON(R6a)(R6b)、—NHCOOR7或—CONHR8所表示的基团，其中R4、R5、R6a、R6b、R7和R8分别是氢原子、可选取代的碳氢基团、可选取代的杂环基团等，环A是单环芳香环，可选地进一步具有取代基，R1a和R1b可选择性地连接在一起形成可选取代的含氮非芳香杂环，或其盐或前药。本发明的凝血酶受体拮抗剂具有凝血酶受体（特别是PAR-1）拮抗作用，可用于预防或治疗PAR-1介导的病理状态或疾病。
• Triazole derivative and use thereof
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US07803822B2

  公开（公告）日：2010-09-28

  The present invention relates to a thrombin receptor antagonist containing a compound represented by the formula (I) wherein R1a, R1b and R2 are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted alkoxy, R3 is a group represented by the formula —NHCOR4, —NHSO2R5, —NHCON(R6a)(R6b), —NHCOOR7 or —CONHR8 wherein R4, R5, R6a, R6b, R7 and R8 are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like), ring A is monocyclic aromatic ring optionally further having substituent(s), R1a and R1b are optionally bonded to each other to form an optionally substituted nitrogen-containing non-aromatic heterocycle, or a salt thereof or a prodrug thereof. The thrombin receptor antagonist of the present invention has a thrombin receptor (particularly PAR-1) antagonistic action and is useful for the prophylaxis or treatment of PAR-1 mediated pathological condition or disease.

  本发明涉及含有式(I)所表示的化合物的凝血酶受体拮抗剂，其中R1a、R1b和R2分别是氢原子、可选取代的碳氢基团、可选取代的杂环基团或可选取代的烷氧基，R3是由式—NHCOR4、—NHSO2R5、—NHCON(R6a)(R6b)、—NHCOOR7或—CONHR8所表示的基团，其中R4、R5、R6a、R6b、R7和R8分别是氢原子、可选取代的碳氢基团、可选取代的杂环基团等，环A是单环芳香环，可选地进一步具有取代基，R1a和R1b可选地相互连接以形成可选取代的含氮非芳香杂环，或其盐或前药。本发明的凝血酶受体拮抗剂具有凝血酶受体（特别是PAR-1）拮抗作用，可用于预防或治疗PAR-1介导的病理状态或疾病。
• TRIAZOLE DERIVATIVE AND THE USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1867331A1

  公开（公告）日：2007-12-19

  The present invention relates to a thrombin receptor antagonist containing a compound represented by the formula (I) wherein R1a, R1b and R2 are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted alkoxy, R3 is a group represented by the formula -NHCOR4, -NHSO2R5, -NHCON(R6a) (R6b), -NHCOOR7 or -CONHR8 wherein R4, R5, R6a, R6b, R7 and R8 are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like), ring A is monocyclic aromatic ring optionally further having substituent(s), R1a and R1b are optionally bonded to each other to form an optionally substituted nitrogen-containing non-aromatic heterocycle, or a salt thereof or a prodrug thereof. The thrombin receptor antagonist of the present invention has a thrombin receptor (particularly PAR-1) antagonistic action and is useful for the prophylaxis or treatment of PAR-1 mediated pathological condition or disease.

  本发明涉及一种凝血酶受体拮抗剂，其中含有由式（I）代表的化合物 其中 R1a、R1b 和 R2 各为氢原子、任选取代的烃基、任选取代的杂环基团或任选取代的烷氧基，R3 为由式 -NHCOR4、-NHSO2R5、-NHCON(R6a) (R6b)、-NHCOOR7 或 -CONHR8 所代表的基团，其中 R4、R5、R6a、R6b、R7 和 R8 各为氢原子、任选取代的烃基、任选取代的杂环基等），环 A 是单环芳香环，任选进一步具有取代基，R1a 和 R1b 任选相互键合以形成任选取代的含氮非芳香杂环，或其盐或其原药。本发明的凝血酶受体拮抗剂具有凝血酶受体（尤其是 PAR-1）拮抗作用，可用于预防或治疗 PAR-1 介导的病理状态或疾病。
• EP1867331
  申请人：——

  公开号：——

  公开（公告）日：——
• US7803822B2
  申请人：——

  公开号：US7803822B2

  公开（公告）日：2010-09-28