4-(3-methoxyphenyl)amino-5,6-tetramethylenothieno<2,3-d>pyrimidine | 81136-48-3

• 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: 4-(3-methoxyphenyl)amino-5,6-tetramethylenothieno<2,3-d>pyrimidine
• 英文别名: N-(3-methoxyphenyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine；(3-methoxy-phenyl)-(5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d]pyrimidine-4-yl)-amine；4-(3-methoxyphenyl)amino-5,6-tetramethylenothieno[2,3-d]pyrimidine；N-(3-methoxyphenyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-amine；N-(3-methoxyphenyl)-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-amine
• CAS: 81136-48-3
• 化学式: C₁₇H₁₇N₃OS
• mdl: MFCD00401695
• 分子量: 311.407
• InChiKey: GYFVTEAYJLVNMX-UHFFFAOYSA-N

物化性质

• 熔点：
  110-111 °C
• 沸点：
  518.5±50.0 °C(Predicted)
• 密度：
  1.317±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  5

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 4-(3-methoxyphenyl)amino-5,6-tetramethylenothieno<2,3-d>pyrimidine
  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

• [EN] THERAPEUTIC APPLICATION OF TRICICLIC AROMATIC AND SATURATED BENZO(4,5)THIENO-(2,3-D)PYRIMIDINE DERIVATES, AS WELL AS THEIR THERAPEUTICALLY ACCEPTABLE SALTS<br/>[FR] APPLICATION THÉRAPEUTIQUE DE DÉRIVÉS TRICYCLIQUES AROMATIQUES ET SATURÉS DE LA BENZO(4,5)THIÉNO-(2,3-D)PYRIMIDINE, ET LEURS SELS THÉRAPEUTIQUEMENT ACCEPTABLES
  申请人：VICHEM CHEMIE KUTATO KFT

  公开号：WO2009104027A1

  公开（公告）日：2009-08-27

  The subject of the invention is therapeutic application of tricyclic aromatic and saturated benzo[4,5]thieno[2,3-d]pyrimidine derivatives and their therapeutically acceptable salts. The compounds according to the invention is used particularly as active agent of therapeutic preparations of tyrosine-kinase inhibiting action.

  本发明涉及三环芳香和饱和苯并[4,5]噻吩[2,3-d]嘧啶衍生物及其治疗上可接受的盐的治疗应用。根据本发明的化合物特别用作酪氨酸激酶抑制作用的治疗制剂的活性成分。
• Ram; Pandey; Vlietinck, Journal of Heterocyclic Chemistry, 1981, vol. 18, # 7, p. 1277 - 1280
  作者：Ram、Pandey、Vlietinck

  DOI：——

  日期：——
• 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：——
• RAM, VISHNU, J.;PANDEY, HASHI, KESH;VLIETINCK, A. J., J. HETEROCYCL. CHEM., 1981, 18, N 7, 1277-1280
  作者：RAM, VISHNU, J.、PANDEY, HASHI, KESH、VLIETINCK, A. J.

  DOI：——

  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.