3-(2-methylsulfonylpyrimidin-4-yl)-1H-pyrrolo[2,3-b]pyridine

• 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: 3-(2-methylsulfonylpyrimidin-4-yl)-1H-pyrrolo[2,3-b]pyridine
• 化学式: C₁₂H₁₀N₄O₂S
• 分子量: 274.303
• InChiKey: NZNGPNHDYXHWQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  97
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2-methylsulfonylpyrimidin-4-yl)-1H-pyrrolo[2,3-b]pyridine 、 2-(4-甲氧苯基)乙胺 以 四氢呋喃 为溶剂， 生成 N-(4-methoxyphenethyl)-4-(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
• 作为产物：
  描述：

  3-碘-7-氮杂吲哚 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 caesium carbonate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 41.0h， 生成 3-(2-methylsulfonylpyrimidin-4-yl)-1H-pyrrolo[2,3-b]pyridine
  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

• Azaindoles useful as inhibitors of JAK and other protein kinases
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：EP2786995A1

  公开（公告）日：2014-10-08

  The present invention relates to compounds of formula (I), which are inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  本发明涉及作为蛋白激酶抑制剂的式(I)化合物。本发明还提供了包含本发明化合物的药物组合物以及使用该组合物治疗各种疾病的方法。
• Azaindoles useful as inhibitors of jak and other protein kinases
  申请人：Vertex Pharmaceuticals Inc.

  公开号：EP2311837B1

  公开（公告）日：2014-05-21
• Design of Novel 3-Pyrimidinylazaindole CDK2/9 Inhibitors with Potent In Vitro and In Vivo Antitumor Efficacy in a Triple-Negative Breast Cancer Model
  作者：Umed Singh、Gousia Chashoo、Sameer U. Khan、Priya Mahajan、Amit Nargotra、Girish Mahajan、Amarinder Singh、Anjna Sharma、Mubashir J. Mintoo、Santosh Kumar Guru、Hariprasad Aruri、Thanusha Thatikonda、Promod Sahu、Pankaj Chibber、Vikas Kumar、Sameer A. Mir、Sonali S. Bharate、Sreedhar Madishetti、Utpal Nandi、Gurdarshan Singh、Dilip Manikrao Mondhe、Shashi Bhushan、Fayaz Malik、Serge Mignani、Ram A. Vishwakarma、Parvinder Pal Singh

  DOI：10.1021/acs.jmedchem.7b00663

  日期：2017.12.14

  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.