N-[(2Z)-4-(5-methyl-2,4-dioxo-3H-pyrimidin-1-yl)but-2-en-1-yl]-2,2-diphenylacetamide

• 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: N-[(2Z)-4-(5-methyl-2,4-dioxo-3H-pyrimidin-1-yl)but-2-en-1-yl]-2,2-diphenylacetamide
• 英文别名: N-[4-(5-Methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-but-2-enyl]-2,2-diphenyl-acetamide；N-[(Z)-4-(5-methyl-2,4-dioxopyrimidin-1-yl)but-2-enyl]-2,2-diphenylacetamide
• 化学式: C₂₃H₂₃N₃O₃
• 分子量: 389.454
• InChiKey: NDILRUMMGDBGQL-HJWRWDBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  78.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  胸腺嘧啶 在 N,O-双三甲硅基乙酰胺 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 一水合肼 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 N-[(2Z)-4-(5-methyl-2,4-dioxo-3H-pyrimidin-1-yl)but-2-en-1-yl]-2,2-diphenylacetamide
  参考文献：
  名称：

  Improving the selectivity of acyclic nucleoside analogues as inhibitors of human mitochondrial thymidine kinase: replacement of a triphenylmethoxy moiety with substituted amines and carboxamides

  摘要：

  Two series of analogues of the novel human mitochondrial thymidine kinase inhibitor 1-[(Z)-4-(triphenylmethoxy)-2butenyl]thymine were synthesized by replacing the triphenylmethoxy moiety by a variety of substituted amines and carboxamides. In all the bases, the selectivity against the mitochondrial enzyme was either maintained or improved, and several derivatives were almost as potent as the parent compound. A molecular model was built that can account for the observed selectivities. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00639-5

文献信息

• Thymine derivatives and quinazoline-dione derivatives for the inhibition of HSP27
  申请人：TECHNISCHE UNIVERSITAET DRESDEN

  公开号：US10940150B2

  公开（公告）日：2021-03-09

  The present invention relates to novel HSP27 inhibitors, in particular thymine derivatives according to general formula (VI), (VII) or (VII) and phenothiazine derivatives according to formula (V), and to their use as drugs for the selective inhibition of the heat shock protein HSP27 (HSPB1), in particular for use in the treatment of carcinomas or cystic fibrosis, said inhibitors having a particularly advantageous activity in the lower micromolar or sub-micromolar active ingredient concentration range with respect to HSP27.

  本发明涉及新型HSP27抑制剂，特别是根据通式（VI）、（VII）或（VII）的胸腺嘧啶衍生物和根据式（V）的吩噻嗪衍生物，以及它们作为选择性抑制热休克蛋白HSP27（HSPB1）的药物的用途，特别是用于治疗癌症或囊性纤维化，所述抑制剂在较低的微摩尔或亚微摩尔活性成分浓度范围内对HSP27具有特别有利的活性。
• EFFICIENT INHIBITION OF HSP27
  申请人：TECHNISCHE UNIVERSITAET DRESDEN

  公开号：US20170216297A1

  公开（公告）日：2017-08-03

  The present invention relates to novel HSP27 inhibitors, in particular purine derivatives according to general formula (I) or (II) and phenothiazine derivatives according to formula (V), and to their use as drugs for the selective inhibition of the heat shock protein HSP27 (HSPB1), in particular for use in the treatment of carcinomas or cystic fibrosis, said inhibitors having a particularly advantageous activity in the lower micromolar or sub-micromolar active ingredient concentration range with respect to HSP2.
• THYMINE DERIVATIVES AND QUINAZOLINE-DIONE DERIVATIVES FOR THE INHIBITION OF HSP27
  申请人：TECHNISCHE UNIVERSITAET DRESDEN

  公开号：US20180207160A1

  公开（公告）日：2018-07-26

  The present invention relates to novel HSP27 inhibitors, in particular thymine derivatives according to general formula (VI), (VII) or (VII) and phenothiazine derivatives according to formula (V), and to their use as drugs for the selective inhibition of the heat shock protein HSP27 (HSPB1), in particular for use in the treatment of carcinomas or cystic fibrosis, said inhibitors having a particularly advantageous activity in the lower micromolar or sub-micromolar active ingredient concentration range with respect to HSP27.
• [DE] EFFIZIENTE HEMMUNG VON HSP27<br/>[EN] EFFICIENT INHIBITION OF HSP27<br/>[FR] INHIBITION EFFICACE DE HSP27
  申请人：UNIV DRESDEN TECH

  公开号：WO2016016267A1

  公开（公告）日：2016-02-04

  Die vorliegende Erfindung betrifft neuartige HSP27-lnhibitoren, insbesondere Purin-Derivate gemäß der allgemeinen Formel (I) bzw. (II) und Phenothiazin-Derivaten gemäß der Formel (V) sowie deren Verwendung als Arzneimittel für die selektive Inhibierung des Hitzeschockproteins HSP27 (HSPB1), insbesondere für die Verwendung zur Behandlung von Karzinomen oder Mukoviszidose, wobei diese Inhibitoren gegenüber HSP27 besonders vorteilhaft eine Aktivität im unteren mikromolaren bzw. submikromolaren Wirkstoff konzentrationsbereich aufweisen.
• [DE] THYMIN- UND CHINAZOLIN-DION-DERIVATE ZUR HEMMUNG VON HSP27<br/>[EN] THYMINE DERIVATIVES AND QUINAZOLINE-DIONE DERIVATIVES FOR THE INHIBITION OF HSP27<br/>[FR] DÉRIVÉS DE LA THYMINE ET DE LA CHINAZOLINE-DIONE POUR INHIBER HSP27
  申请人：UNIV DRESDEN TECH

  公开号：WO2016016268A1

  公开（公告）日：2016-02-04

  Die vorliegende Erfindung betrifft neuartige HSP27-Inhibitoren, insbesondere Thymin- Derivate gemäß der allgemeinen Formel(VI), (VII)bzw. (VIII) und Phenothiazin-Derivaten gemäß der Formel(V) sowie deren Verwendung als Arzneimittel für die selektive Inhibierung des Hitzeschockproteins HSP27 (HSPB1), insbesonderefür die Verwendung zur Behandlung von Karzinomen oder Mukoviszidose, wobei diese Inhibitoren gegenüber HSP27 besonders vorteilhaft eine Aktivität im unteren mikromolaren bzw. submikromolaren Wirkstoffkonzentrationsbereich aufweisen.