N-(4-bromophenyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine | 293766-33-3

• 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: N-(4-bromophenyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine
• 英文别名: (4-bromo-phenyl)-(5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidine-4-yl)-amine；N-(4-bromophenyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-amine
• CAS: 293766-33-3
• 化学式: C₁₆H₁₄BrN₃S
• 分子量: 360.277
• InChiKey: TXADWVKFIMBTST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5,6,7,8-四氢-[1]-苯并噻吩[2,3-d]嘧啶-4(1h)-酮 在 氯化亚砜 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 N-(4-bromophenyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 4-aniline-thieno[2,3-d]pyrimidine derivatives as MNK1 inhibitors against renal cell carcinoma and nasopharyngeal carcinoma

  摘要：

  MAP Kinase Interacting Serine/Threonine Kinase 1 (MNK1) play important roles in the signaling transduction of MAPK pathways. It is significantly overexpressed in renal clear cell carcinoma and head-neck squamous cell carcinoma tissues in both mRNA and protein levels. Based on the crystallographic structure of MNK1 protein and binding modes analysis of known MNK inhibitors, we have designed and synthesized a series of 4-aniline-thieno [2,3-d] pyrimidine derivatives as potential MNK1 inhibitors. These synthetic compounds are tested in biochemical and cell proliferation assays, and six of them display potent inhibitory capacity against MNK1 kinase and cancer cell lines. Compound 12dj with strongest inhibitory capacity is transferred to molecular mechanism studies, and the results indicated that 12dj remarkably suppresses the phosphorylation of EIF4E, a substrate of MNK1. And the expression levels of MNK1, ERK1/2 and pERK1/2 are not affected by compound 12dj incubation in SUNE-1 and 786-O cells. In summary, our works suggested that these novel 4-aniline-thieno[2,3-d]pyrimidine based MNK1 inhibitors might be attractive lead compounds for targeted therapy of renal cell carcinoma and nasopharyngeal carcinoma.

  DOI：

  10.1016/j.bmc.2019.04.022

文献信息

• Microwave-based synthesis of novel thienopyrimidine bioisosteres of gefitinib
  作者：Manisha S. Phoujdar、Muthu K. Kathiravan、Jitender B. Bariwal、Anamik K. Shah、Kishor S. Jain

  DOI：10.1016/j.tetlet.2007.11.135

  日期：2008.2

  A series of novel 2-unsubstituted 4-(substituted)anilinothieno[2,3-d]pyrimidines is synthesized through the chlorination of the corresponding 2-unsubstituted-thieno[2,3-d]-pyrimidin-4-ones, followed by the nucleophilic displacement of the 4-Cl group of 9, with a variety of anilines. All four steps of this synthesis involve microwave irradiation (MWI) and the entire synthesis requires only 2 h. (c) 2007 Elsevier Ltd. All rights reserved.
• Novel Dual Use of Formamide-POCl₃ Mixture for the Efficient, One-Pot Synthesis of Condensed 2<i>H</i>-Pyrimidin-4-amine Libraries Under Microwave Irradiation
  作者：Kishore S. Jain、Muthu K. Kathiravan、Jitender B. Bariwal、Pratip K. Chaskar、Santosh S. Tompe、Nikhilesh Arya

  DOI：10.1080/00397911.2011.607934

  日期：2013.1.1

  The novel dual use of formamide-POCl3 mixture for the incorporation of a C-N fragment to form the pyrimidine nucleus and its subsequent chlorination in an efficient, one-pot synthesis of potentially bioactive condensed 2H-pyrimidin-4-amine libraries under microwave irradiation (MWI) is reported. The one-pot microwave-assisted synthetic protocol is high-yielding, ecofriendly, rapid, and novel as well as eliminates intermittent work-ups. The protocol can be adapted for the library synthesis of series of a condensed pyrimidines.
• A Microwave-Enhanced Synthesis and Biological Evaluation of N-Aryl‑5,6,7,8‑tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amines
  作者：Qing Han、Zijian Yin、Jingjiao Sui、Qingming Wang、Yaquan Sun

  DOI：10.21577/0103-5053.20190044

  日期：——
• Design, synthesis and biological evaluation of 4-aniline-thieno[2,3-d]pyrimidine derivatives as MNK1 inhibitors against renal cell carcinoma and nasopharyngeal carcinoma
  作者：Min Zhang、Li Jiang、Jia Tao、Zhaoping Pan、Mingyao He、Dongyuan Su、Gu He、Qinglin Jiang

  DOI：10.1016/j.bmc.2019.04.022

  日期：2019.6

  MAP Kinase Interacting Serine/Threonine Kinase 1 (MNK1) play important roles in the signaling transduction of MAPK pathways. It is significantly overexpressed in renal clear cell carcinoma and head-neck squamous cell carcinoma tissues in both mRNA and protein levels. Based on the crystallographic structure of MNK1 protein and binding modes analysis of known MNK inhibitors, we have designed and synthesized a series of 4-aniline-thieno [2,3-d] pyrimidine derivatives as potential MNK1 inhibitors. These synthetic compounds are tested in biochemical and cell proliferation assays, and six of them display potent inhibitory capacity against MNK1 kinase and cancer cell lines. Compound 12dj with strongest inhibitory capacity is transferred to molecular mechanism studies, and the results indicated that 12dj remarkably suppresses the phosphorylation of EIF4E, a substrate of MNK1. And the expression levels of MNK1, ERK1/2 and pERK1/2 are not affected by compound 12dj incubation in SUNE-1 and 786-O cells. In summary, our works suggested that these novel 4-aniline-thieno[2,3-d]pyrimidine based MNK1 inhibitors might be attractive lead compounds for targeted therapy of renal cell carcinoma and nasopharyngeal carcinoma.