4-chloro-6-(4-hydroxyphenyl)-5-methyl-2-(thiophen-2-yl)thieno[2,3-d]pyrimidine | 949528-07-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 4-chloro-6-(4-hydroxyphenyl)-5-methyl-2-(thiophen-2-yl)thieno[2,3-d]pyrimidine
• 英文别名: 4-(4-chloro-5-methyl-2-thiophen-2-yl-thieno[2,3-d]pyrimidin-6-yl)-phenol；4-(4-Chloro-5-methyl-2-thiophen-2-ylthieno[2,3-d]pyrimidin-6-yl)phenol；4-(4-chloro-5-methyl-2-thiophen-2-ylthieno[2,3-d]pyrimidin-6-yl)phenol
• CAS: 949528-07-8
• 化学式: C₁₇H₁₁ClN₂OS₂
• 分子量: 358.872
• InChiKey: HVGVKIFOVGOJRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-chloro-6-(4-hydroxyphenyl)-5-methyl-2-(thiophen-2-yl)thieno[2,3-d]pyrimidine 在 一水合肼 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 生成
  参考文献：
  名称：

  Synthesis and biological evaluation of novel thieno[2,3-d]pyrimidine-based FLT3 inhibitors as anti-leukemic agents

  摘要：

  The most common mutations in acute myeloid leukemia (AML) are those that cause the activation of FMS-like tyrosine kinase 3 (FLT3). Therefore, FLT3 is regarded as a potential target for the treatment of AML A novel series of thieno[2,3-d]pyrimidine-based analogs was designed and synthesized as FLT3 inhibitors. All synthesized compounds were assayed for the tyrosine kinase activity of FLT3 and growth inhibitory activity in four human leukemia cell lines (THP1, MV4-11, K562, and HL-60). Among these compounds, compound 17a, which possesses relatively short and simple substituents at the C-6 position of thieno[2,3-d]pyrimidine, emerged as the most promising anti-leukemic agent. Compound 17a exhibited potent inhibition of FLT3-positive leukemic cell growth and of the FLT3 D835Y kinase; such inhibition is required for the successful treatment of AML. The data supports the further investigation of this class of compounds as potential anti-leukemic agents. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.08.001
• 作为产物：
  描述：

  对甲氧基苯基丙酮 在 盐酸 、 三溴化硼 、 sulfur 、 二乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 反应 63.0h， 生成 4-chloro-6-(4-hydroxyphenyl)-5-methyl-2-(thiophen-2-yl)thieno[2,3-d]pyrimidine
  参考文献：
  名称：

  WO2007/102679

  摘要：

  公开号：

文献信息

• Structural modifications at the 6-position of thieno[2,3-d]pyrimidines and their effects on potency at FLT3 for treatment of acute myeloid leukemia
  作者：Hyuntae Kim、Chulho Lee、Jee Sun Yang、Seonghwi Choi、Chun-Ho Park、Jong Soon Kang、Soo Jin Oh、Jieun Yun、Myung-Hwa Kim、Gyoonhee Han

  DOI：10.1016/j.ejmech.2016.05.022

  日期：2016.9

  Fms-like tyrosine kinase 3 (FLT3) is a well-known and important target for the treatment of acute myeloid leukemia (AML). A series of thieno[2,3-d]pyrimidine derivatives from a modification at the 6-position were synthesized to identify effective FLT3 inhibitors. Although compounds 1 and 2 emerged as promising FLT3 inhibitors among the synthesized compounds, both compounds exhibited poor metabolic

  Fms样酪氨酸激酶3（FLT3）是治疗急性髓细胞性白血病（AML）的众所周知且重要的靶标。合成了一系列在6-位修饰的噻吩并[2,3- d ]嘧啶衍生物，以鉴定有效的FLT3抑制剂。尽管在合成的化合物中化合物1和2成为有前途的FLT3抑制剂，但两种化合物在人和大鼠肝微粒体中均显示出较差的代谢稳定性。因此，需要进一步优化以发现FLT3抑制剂，重点是改善代谢稳定性。化合物16d具有在5位甲基和在6位4-（2-甲基氨基乙氧基）苯基的结构修饰的化合物，对FLT3表现出良好的抑制活性，并且对包括MV4在内的四种白血病细胞系表现出有效的抗增殖活性-11。此外，化合物16d显示出增强的代谢稳定性。这项研究的结果表明，16d作为有效的FLT3抑制剂可能是有希望用于进一步优化和开发的化合物。
• [EN] NOVEL THIENOPYRIMIDINE DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME<br/>[FR] NOUVEAUX DÉRIVÉS DE LA THIÉNOPYRIMIDINE OU LEURS SELS PHARMACOCOMPATIBLES, LEUR PROCÉDÉ DE PRÉPARATION, ET PRÉPARATIONS PHARMACEUTIQUES LES COMPRENANT
  申请人：JE IL PHARMACEUTICAL CO LTD

  公开号：WO2007102679A1

  公开（公告）日：2007-09-13

  [EN] The present invention relates to a novel thienopyrimidine derivative having an excellent anti¬ inflammatory and anti-cancer activity, or a pharmaceutically acceptable salt thereof, a process for the preparation thereof and a pharmaceutical composition comprising the same. The compound according to the present invention strongly inhibits IKB kinase-ß (IKK-ß) involved in the activation of a transcriptional factor, NF-?B, which is associated with inducing various immune and inflammatory diseases, whereby a composition comprising the compound is a useful therapeutic agent against inflammatory diseases, in particular, arthritis and cancer.
  [FR] L'invention porte sur un nouveau dérivé de la thiénopyrimidine présentant une excellente activité anti- inflammatoire et anti-cancéreuse ou ses dérivés pharmacocompatibles, sur son procédé de préparation, et sur des préparations pharmaceutiques les comprenant. Ce composé inhibe fortement la kinase IKB-ß (IKK-ß) impliquée dans l'activation d'un facteur de transcription, le NF-?B, associé à l'induction de différentes maladies immunes et inflammatoires; les préparations le comprenant sont donc utiles contre les maladies inflammatoires dont en particulier l'arthrite et le cancer.