4-amino-5-(3-cyanobenzoyl)-2-[(propan-2-yl)amino]thiophene-3-carbonitrile

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-amino-5-(3-cyanobenzoyl)-2-[(propan-2-yl)amino]thiophene-3-carbonitrile
• 英文别名: 4-Amino-5-(3-cyanobenzoyl)-2-(propan-2-ylamino)thiophene-3-carbonitrile；4-amino-5-(3-cyanobenzoyl)-2-(propan-2-ylamino)thiophene-3-carbonitrile
• 化学式: C₁₆H₁₄N₄OS
• 分子量: 310.379
• InChiKey: YGAYPNUDKXPTOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  异硫氰酸异丙酯 、 3-(2-溴乙酰基)苯甲腈 、 丙二腈 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以73%的产率得到4-amino-5-(3-cyanobenzoyl)-2-[(propan-2-yl)amino]thiophene-3-carbonitrile
  参考文献：
  名称：

  5-Keto-3-cyano-2,4-diaminothiophenes as selective maternal embryonic leucine zipper kinase inhibitors

  摘要：

  Maternal embryonic leucine zipper kinase (MELK) is involved in several key cellular processes and displays increased levels of expression in numerous cancer classes (colon, breast, brain, ovary, prostate and lung). Although no selective MELK inhibitors have yet been approved, increasing evidence suggest that inhibition of MELK would constitute a promising approach for cancer therapy. A weak high-throughput screening hit (17, IC50 approximate to 5 mu M) with lead-like properties was optimized for MELK inhibition. The early identification of a plausible binding mode by molecular modeling offered guidance in the choice of modifications towards compound 52 which displayed a 98 nM IC50. A good selectivity profile was achieved for a representative member of the series (29) in a 486 protein kinase panel. Future elaboration of 52 has the potential to deliver compounds for further development with chemotherapeutic aims.

  DOI：

  10.1016/j.bmcl.2018.12.051

文献信息

• 5-Keto-3-cyano-2,4-diaminothiophenes as selective maternal embryonic leucine zipper kinase inhibitors
  作者：Nicolas Boutard、Aleksandra Sabiniarz、Klaudia Czerwińska、Małgorzata Jarosz、Anna Cierpich、Ewa Kolasińska、Katarzyna Wiklik、Karolina Gluza、Claude Commandeur、Anna Buda、Agata Stasiowska、Aneta Bobowska、Mariusz Galek、Charles-Henry Fabritius、Marta Bugaj、Edyta Palacz、Andrzej Mazan、Adrian Zarębski、Karolina Krawczyńska、Małgorzata Żurawska、Przemysław Zawadzki、Mariusz Milik、Paulina Węgrzyn、Monika Dobrzańska、Krzysztof Brzózka、Piotr Kowalczyk

  DOI：10.1016/j.bmcl.2018.12.051

  日期：2019.2

  Maternal embryonic leucine zipper kinase (MELK) is involved in several key cellular processes and displays increased levels of expression in numerous cancer classes (colon, breast, brain, ovary, prostate and lung). Although no selective MELK inhibitors have yet been approved, increasing evidence suggest that inhibition of MELK would constitute a promising approach for cancer therapy. A weak high-throughput screening hit (17, IC50 approximate to 5 mu M) with lead-like properties was optimized for MELK inhibition. The early identification of a plausible binding mode by molecular modeling offered guidance in the choice of modifications towards compound 52 which displayed a 98 nM IC50. A good selectivity profile was achieved for a representative member of the series (29) in a 486 protein kinase panel. Future elaboration of 52 has the potential to deliver compounds for further development with chemotherapeutic aims.