5-phenyl-2-thiophen-2-yl-3H-thieno[2,3-d]pyrimidin-4-one | 852933-90-5

• 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-phenyl-2-thiophen-2-yl-3H-thieno[2,3-d]pyrimidin-4-one
• CAS: 852933-90-5
• 化学式: C₁₆H₁₀N₂OS₂
• 分子量: 310.4
• InChiKey: DAEMMBDNRXPPRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  97.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-phenyl-2-thiophen-2-yl-3H-thieno[2,3-d]pyrimidin-4-one 在 一水合肼 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKβ inhibitors

  摘要：

  Inactivation of the NF-kappa B signaling pathway by inhibition of IKK beta is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKb inhibitor, SPC-839, and then biologically evaluated. The resulting analogues had good inhibitory activity against both nitric oxide and TNF-alpha, which are well-known inflammatory responses generated by activated NF-kappa B. However, no inhibitory activity against IKK beta was observed with these compounds. The thienopyrimidine-based analogues were subsequently screened for a target kinase, and FLT3, which is a potential target for acute myeloid leukemia (AML), was identified. Thienopyrimidine-based FLT3 inhibitors showed good inhibition profiles against FLT3 under 1 mu M. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.058
• 作为产物：
  描述：

  Methyl-α-cyano-β-methyl-β-phenylacrylat 在 哌啶 、 盐酸 、 sulfur 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 生成 5-phenyl-2-thiophen-2-yl-3H-thieno[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKβ inhibitors

  摘要：

  Inactivation of the NF-kappa B signaling pathway by inhibition of IKK beta is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKb inhibitor, SPC-839, and then biologically evaluated. The resulting analogues had good inhibitory activity against both nitric oxide and TNF-alpha, which are well-known inflammatory responses generated by activated NF-kappa B. However, no inhibitory activity against IKK beta was observed with these compounds. The thienopyrimidine-based analogues were subsequently screened for a target kinase, and FLT3, which is a potential target for acute myeloid leukemia (AML), was identified. Thienopyrimidine-based FLT3 inhibitors showed good inhibition profiles against FLT3 under 1 mu M. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.058

文献信息

• 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.
• Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKβ inhibitors
  作者：Chun-Ho Park、Chulho Lee、Jee Sun Yang、Bo-Young Joe、Kwangwoo Chun、Hyuntae Kim、Hye Yun Kim、Jong Soon Kang、Jangik I. Lee、Myung-Hwa Kim、Gyoonhee Han

  DOI：10.1016/j.bmcl.2014.04.058

  日期：2014.6

  Inactivation of the NF-kappa B signaling pathway by inhibition of IKK beta is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKb inhibitor, SPC-839, and then biologically evaluated. The resulting analogues had good inhibitory activity against both nitric oxide and TNF-alpha, which are well-known inflammatory responses generated by activated NF-kappa B. However, no inhibitory activity against IKK beta was observed with these compounds. The thienopyrimidine-based analogues were subsequently screened for a target kinase, and FLT3, which is a potential target for acute myeloid leukemia (AML), was identified. Thienopyrimidine-based FLT3 inhibitors showed good inhibition profiles against FLT3 under 1 mu M. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML. (C) 2014 Elsevier Ltd. All rights reserved.