1-[8-(triphenylmethoxy)octyl]thymine | 921587-95-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1-[8-(triphenylmethoxy)octyl]thymine
• 英文别名: 5-methyl-1-(8-trityloxyoctyl)pyrimidine-2,4-dione
• CAS: 921587-95-3
• 化学式: C₃₂H₃₆N₂O₃
• 分子量: 496.649
• InChiKey: SFNKSIIBUILCIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  37
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1,8-辛二醇 在 4-二甲氨基吡啶 、 sodium hydroxide 、 PS-Ph₃P 、 偶氮二甲酸二异丙酯 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 1-[8-(triphenylmethoxy)octyl]thymine
  参考文献：
  名称：

  N-Substituted Thymine Derivatives as Mitochondrial Thymidine Kinase (TK-2) Inhibitors

  摘要：

  Novel N-1-substituted thymine derivatives related to 1-[(Z)-4-(triphenylmethoxy)-2-butenyl]thymine have been synthesized and evaluated against thymidine kinase-2 (TK-2) and related nucleoside kinases [i.e., Drosophila melanogaster deoxynucleoside kinase (Dm-dNK) and herpes simplex virus type 1 thymidine kinase (HSV-1 TK)]. The thymine base has been tethered to a distal triphenylmethoxy moiety through a polymethylene chain (n = 3-8) or through a (2-ethoxy)ethyl spacer. Moreover, substitutions at position 4 of one of the phenyl rings of the triphenylmethoxy moiety have been performed. Compounds with a hexamethylene spacer (18, 26b, 31) displayed the highest inhibitory values against TK-2 (IC50 = 0.3-0.5 mu M). Compound 26b competitively inhibited TK-2 with respect to thymidine and uncompetitively with respect to ATP. A rationale for the biological data was provided by docking some representative inhibitors into a homology-based model of human TK-2. Moreover, two of the most potent TK-2 inhibitors (18 and 26b) that also inhibit HSV-1 TK were able to reverse the cytostatic activity of 1-(beta-D-arabinofuranosyl)thymine (Ara-T) and ganciclovir in HSV-1 TK-expressing OST-TK-/HSV-1 TK+ cell cultures.

  DOI：

  10.1021/jm0610550

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.
• <i>N</i>-Substituted Thymine Derivatives as Mitochondrial Thymidine Kinase (TK-2) Inhibitors
  作者：Ana-Isabel Hernández、Olga Familiar、Ana Negri、Fátima Rodríguez-Barrios、Federico Gago、Anna Karlsson、María-José Camarasa、Jan Balzarini、María-Jesús Pérez-Pérez

  DOI：10.1021/jm0610550

  日期：2006.12.1

  Novel N-1-substituted thymine derivatives related to 1-[(Z)-4-(triphenylmethoxy)-2-butenyl]thymine have been synthesized and evaluated against thymidine kinase-2 (TK-2) and related nucleoside kinases [i.e., Drosophila melanogaster deoxynucleoside kinase (Dm-dNK) and herpes simplex virus type 1 thymidine kinase (HSV-1 TK)]. The thymine base has been tethered to a distal triphenylmethoxy moiety through a polymethylene chain (n = 3-8) or through a (2-ethoxy)ethyl spacer. Moreover, substitutions at position 4 of one of the phenyl rings of the triphenylmethoxy moiety have been performed. Compounds with a hexamethylene spacer (18, 26b, 31) displayed the highest inhibitory values against TK-2 (IC50 = 0.3-0.5 mu M). Compound 26b competitively inhibited TK-2 with respect to thymidine and uncompetitively with respect to ATP. A rationale for the biological data was provided by docking some representative inhibitors into a homology-based model of human TK-2. Moreover, two of the most potent TK-2 inhibitors (18 and 26b) that also inhibit HSV-1 TK were able to reverse the cytostatic activity of 1-(beta-D-arabinofuranosyl)thymine (Ara-T) and ganciclovir in HSV-1 TK-expressing OST-TK-/HSV-1 TK+ cell cultures.