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-carboxamide

• 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: 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-carboxamide
• 英文别名: 5-Methyl-4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-thiophen-2-ylthieno[2,3-d]pyrimidine-6-carboxamide
• 化学式: C₁₇H₁₃N₅O₃S₂
• 分子量: 399.454
• InChiKey: GCAJSUGVGYEWPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  175
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  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-carboxamide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 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-carboxamide 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
• 作为产物：
  描述：

  2-氨在-5-氨基羰基-4-甲基-3-噻吩羧酸乙酯 在 盐酸 、 一水合肼 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 氯仿 为溶剂， 反应 30.0h， 生成 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-carboxamide
  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