methyl 5-methyl-4-(3-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-ylamino)-2-(thiophen-2-yl)thieno[2,3-d]pyrimidine-6-carboxylate hydrochloride

• 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: methyl 5-methyl-4-(3-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-ylamino)-2-(thiophen-2-yl)thieno[2,3-d]pyrimidine-6-carboxylate hydrochloride
• 英文别名: 5-methyl-4-(3-methyl-2,5-dioxo-2,5-dihydro-pyrrol-1-ylamino)-2-thiophen-2-yl-thieno[2,3-d]pyrimidin-6-carboxylic acid methyl ester hydrochloride；Methyl 5-methyl-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-thiophen-2-ylthieno[2,3-d]pyrimidine-6-carboxylate;hydrochloride
• 化学式: C₁₈H₁₄N₄O₄S₂*ClH
• 分子量: 450.926
• InChiKey: HDVIFKPEYKFKHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.58
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  158
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  methyl 4-hydrazineyl-5-methyl-2-(thiophen-2-yl)thieno[2,3-d]pyrimidine-6-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 反应 20.0h， 生成 methyl 5-methyl-4-(3-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-ylamino)-2-(thiophen-2-yl)thieno[2,3-d]pyrimidine-6-carboxylate hydrochloride
  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

文献信息

• [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.
• Synthesis and biological evaluation of novel thieno[2,3-d]pyrimidine-based FLT3 inhibitors as anti-leukemic agents
  作者：Jee Sun Yang、Chun-Ho Park、Chulho Lee、Hwan Kim、Changmok Oh、Yejoo Choi、Jong Soon Kang、Jieun Yun、Jin-Hyun Jeong、Myung-Hwa Kim、Gyoonhee Han

  DOI：10.1016/j.ejmech.2014.08.001

  日期：2014.10

  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.