N²-<3-(hydroxymethyl)phenyl>guanine | 123994-71-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: N²-<3-(hydroxymethyl)phenyl>guanine
• 英文别名: 6H-Purin-6-one, 1,9-dihydro-2-((3-(hydroxymethyl)phenyl)amino)-；2-[3-(hydroxymethyl)anilino]-1,7-dihydropurin-6-one
• CAS: 123994-71-8
• 化学式: C₁₂H₁₁N₅O₂
• 分子量: 257.252
• InChiKey: GOJOULROYGOFSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  102
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N²-<3-(hydroxymethyl)phenyl>guanine 在 sodium azide 、 氢溴酸 作用下， 以 二甲基亚砜 为溶剂， 反应 27.0h， 生成 N²-<3-(azidomethyl)phenyl>guanine
  参考文献：
  名称：

  N2-苯基鸟嘌呤作为单纯疱疹病毒胸苷激酶抑制剂的定量构效关系。

  摘要：

  已开发出Hansch型的定量构效关系，以解释N2-苯基鸟嘌呤对1型和2型单纯疱疹病毒（HSV1,2）的胸苷激酶的抑制作用。在苯环上具有间和/或对位取代基的衍生物作为酶抑制剂表现出很大范围的重叠，但不完全相同。使用36种（HSV1）和35种抑制剂（HSV2）的IC50值来开发使用疏水（pi），电子（sigma，R）和组大小（MR）参数的方程式。对于1型和2型酶的抑制剂，分别获得了相关系数为0.797和0.805的方程式1和2。电位与间取代基的pi值正相关，而与苯环中对位取代基的pi值负相关。通过对位取代基的共振参数R和间位取代基的σ常数也获得正相关。两种酶中最有效的抑制剂是N2- [间-（三氟甲基）苯基]鸟嘌呤，尽管HSV2胸苷激酶比HSV1酶对某些化合物更敏感。

  DOI：

  10.1021/jm00094a007
• 作为产物：
  描述：

  3-氨基苯甲醇 、 2-溴次黄嘌呤 以 乙二醇甲醚 为溶剂， 以36%的产率得到N²-<3-(hydroxymethyl)phenyl>guanine
  参考文献：
  名称：

  Structure-activity relationships of N2-substituted guanines as inhibitors of HSV1 and HSV2 thymidine kinases

  摘要：

  A series of N2-phenylguanines was synthesized and tested for inhibition of the thymidine kinases encoded by Herpes simplex viruses type 1 and type 2. Compounds with hydrophobic, electron-attracting groups in the meta position of the phenyl ring such as m-trifluoromethyl (m-CF3PG, IC50 = 0.1 microM) were the most potent inhibitors of both enzymes. Many derivatives were significantly more potent against the type 2 thymidine kinase, and can effectively discriminate between the two enzymes. Among other N2-substituted guanines, alkyl and benzyl derivatives were moderately potent inhibitors, and the type 2 enzyme was again more sensitive than the type 1 enzyme. None of the compounds inhibited the thymidine kinase isolated from the host HeLa cell line, suggesting that members of this class of compounds may be useful nonsubstrate, antiviral compounds for latent herpesvirus infections.

  DOI：

  10.1021/jm00163a033

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。
• THYMIN- UND CHINAZOLIN-DION-DERIVATE ZUR HEMMUNG VON HSP27
  申请人：Technische Universität Dresden

  公开号：EP3174541A1

  公开（公告）日：2017-06-07
• EFFIZIENTE HEMMUNG VON HSP27
  申请人：Technische Universität Dresden

  公开号：EP3174545A1

  公开（公告）日：2017-06-07
• 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.