4-(5-(benzo[b]thiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 4-(5-(benzo[b]thiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
• 英文别名: 4-[5-(1-benzothiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-2-amine
• 化学式: C₁₉H₁₃N₅S
• 分子量: 343.412
• InChiKey: AJQWHEHMQASSNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苯并噻吩-2-硼酸 在 4-二甲氨基吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 碘 、 potassium carbonate 、 caesium carbonate 、 三乙胺 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(5-(benzo[b]thiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Design of Novel 3-Pyrimidinylazaindole CDK2/9 Inhibitors with Potent In Vitro and In Vivo Antitumor Efficacy in a Triple-Negative Breast Cancer Model

  摘要：

  In the present study, a novel series of 3-pyrimidinylazaindoles were designed and synthesized using a bioinformatics strategy as cyclin-dependent kinases CDK2 and CDK9 inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription. The present approach gives new dimensions to the existing SAR and opens a new opportunity for the lead optimizations from comparatively inexpensive starting materials. The study led to the identification of the alternative lead candidate 4ab with a nanomolar potency against CDK2 and CDK9 and potent antiproliferative activities against a panel of tested tumor cell lines along with a better safety ratio of similar to 33 in comparison to reported leads. In addition, the identified lead 4ab demonstrated a good solubility and an acceptable in vivo PK profile. The identified lead 4ab showed an in vivo efficacy in mouse triple-negative breast cancer (TNBC) syngeneic models with a TGI (tumor growth inhibition) of 90% without any mortality growth inhibition in comparison to reported leads.

  DOI：

  10.1021/acs.jmedchem.7b00663

文献信息

• [EN] 3-PYRIMIDINYL PYRROLO [2,3-B] PYRIDINE AS NEW ANTICANCER AGENTS AND THE PROCESS FOR THE PREPARATION THEREOF<br/>[FR] PYRIDINES 3-PYRIMIDINYL PYRROLO [2,3-B] UTILISÉES COMME NOUVEAUX AGENTS ANTICANCÉREUX ET LEUR PROCÉDÉ DE PRÉPARATION
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2017094026A1

  公开（公告）日：2017-06-08

  The present invention relates to novel 3-pyrimidinyl pyrrolo [2,3-b] pyridine. Particularly, the present invention relates to the preparation of compounds and their anti-cancer activities. More particularly, the present invention relates to new compounds useful as modulators of cyclin-dependent kinase.

  本发明涉及新型的3-嘧啶基吡咯[2,3-b]吡啶。特别地，本发明涉及化合物的制备及其抗癌活性。更具体地说，本发明涉及新化合物，其作为细胞周期依赖性激酶调节剂具有用途。
• 3-PYRIMIDINYL PYRROLO [2,3-B] PYRIDINE AS ANTICANCER AGENTS AND THE PROCESS FOR THE PREPARATION THEREOF
  申请人：Council Of Scientific & Industrial Research

  公开号：EP3383875B1

  公开（公告）日：2022-02-09