N-[2-(dimethylamino)ethyl]-3-hydroxy-4-nitrobenzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: N-[2-(dimethylamino)ethyl]-3-hydroxy-4-nitrobenzamide
• 化学式: C₁₁H₁₅N₃O₄
• 分子量: 253.258
• InChiKey: KEWMBWZZHHWVCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  98.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[2-(dimethylamino)ethyl]-3-hydroxy-4-nitrobenzamide 在 铁粉 、 溶剂黄146 作用下， 反应 2.0h， 生成 4-amino-N-[2-(dimethylamino)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-硝基苯甲酸甲酯 、 N,N-二甲基乙二胺 以 甲醇 为溶剂， 反应 12.0h， 以93%的产率得到N-[2-(dimethylamino)ethyl]-3-hydroxy-4-nitrobenzamide
  参考文献：
  名称：

  [EN] MACROCYCLIC COMPOUNDS AS IRAK4 INHIBITORS FOR THE TREATMENT OF INFLAMMATORY DISEASES
  [FR] COMPOSÉS MACROCYCLIQUES EN TANT QU'INHIBITEURS DE IRAK4 POUR LE TRAITEMENT DE MALADIES INFLAMMATOIRES

  摘要：

  提供的是Formula (I)的化合物，或其药用盐，其中i.a.环A是苯基或5-至6-成员杂芳基；环B是苯基，5-至6-成员杂环烷基或5-至6-成员杂芳基；R4不存在，杂芳基，芳基，C1-3烷基，或R4和R3与它们结合的氮一起形成3-至7-成员杂环烷基环；R5不存在，C(0)NR51，NR52或0；R6是C2-10烷基或烯烃基，其中烷基链中的一个或两个碳原子可以选择性地被0、S、SO、SO2或NR61取代，烷基链中的两个碳原子可以选择性地通过一个两个或三个碳原子的烷基链连接在一起形成5-至7-成员环；R7不存在，NR71或O。这些化合物是对治疗炎症性疾病有用的IRAK4抑制剂。

  公开号：

  WO2014143672A1

文献信息

• MACROCYCLIC COMPOUNDS AS IRAK4 INHIBITORS FOR THE TREATMENT OF INFLAMMATORY DISEASES
  申请人：BIOGEN MA INC.

  公开号：US20160002265A1

  公开（公告）日：2016-01-07

  Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein i.a. Ring A is phenylene or 5- to 6-membered heteroarylene; Ring B is phenylene, 5- to 6-membered heterocycloalkylene or 5- to 6-membered heteroarylen; R 4 is absent, heteroarylene, arylene, C1-3 alkylene, or R 4 and R 3 taken together with the nitrogen to which they are bound form a 3- to 7-membered heterocycloalkyl ring; R 5 is absent, C(0)NR 51 , NR 52 or 0; R 6 is C2-10 alkylene or alkenylene, wherein one or two of the carbon atoms in the alkylene chain is optionally replaced by an 0, S, SO, SO 2 or NR 61 , and wherein two of the carbon atoms in the alkylene chain are optionally connected by a two or three carbon atom alkylene chain to form a 5- to 7-membered ring; R 7 is absent, NR 71 or O. The compounds are IRAK4 inhibitors useful for the treatment of inflammatory diseases.
• US9617282B2
  申请人：——

  公开号：US9617282B2

  公开（公告）日：2017-04-11