5-[4-(trifluoromethyl)phenyl]-1H-pyrrolo[2,3-b]pyridine | 1425411-63-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-[4-(trifluoromethyl)phenyl]-1H-pyrrolo[2,3-b]pyridine
• CAS: 1425411-63-7
• 化学式: C₁₄H₉F₃N₂
• 分子量: 262.234
• InChiKey: IFHRJQPLHFSYRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-[4-(trifluoromethyl)phenyl]-1H-pyrrolo[2,3-b]pyridine 在 potassium phosphate 、 copper(l) iodide 、 sodium cyanoborohydride 、 对甲苯磺酸 、 (1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 3-(3-(5-(4-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)benzylamino)benzoic acid
  参考文献：
  名称：

  Using ‘biased-privileged’ scaffolds to identify lysine methyltransferase inhibitors

  摘要：

  Methylation of histones by lysine methyltransferases (KMTases) plays important roles in regulating chromatin function. It is also now clear that improper KMTases activity is linked to human diseases, such as cancer. We report an approach that employs drug-like 'privileged' scaffolds biased with motifs present in S-adenosyl methionine, the cofactor used by KMTases, to efficiently generate inhibitors for Set7, a biochemically well-characterized KMTase. Setin-1, the most potent inhibitor of Set7 we have developed also inhibits the KMTase G9a. Together these data suggest that these inhibitors should provide good starting points to generate useful probes for KMTase biology and guide the design of KMTase inhibitors with drug-like properties. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.024
• 作为产物：
  描述：

  4-三氟甲基苯硼酸 、 5-溴-7-氮杂吲哚 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 24.0h， 以52.88%的产率得到5-[4-(trifluoromethyl)phenyl]-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  选定的7-氮杂吲哚衍生物作为CDK9 / Cyclin T和Haspin抑制剂的合成及生物学评估

  摘要：

  7-氮杂吲哚支架由于其在疾病相关蛋白激酶抑制剂设计中的价值而备受关注。但是，该支架尚未针对单倍体生殖细胞特异性核蛋白激酶（Haspin）进行评估。本文中，我们报告了一组7-氮杂吲哚衍生物的合成及其对Haspin的评价。还针对CDK9 /细胞周期蛋白T激酶评估了化合物。7-氮杂吲哚衍生物的合成是通过使用适当的卤代7-氮杂吲哚和硼酸的Suzuki偶联而实现的。所筛选的化合物中的七个在纳摩尔至低微摩尔范围内表现出作为CDK9 / Cyclin T和/或Haspin抑制剂的活性。最有前途的双重抑制化合物18c对CDK9 / Cyclin T的抑制潜力为0.206 µM，对Haspin的抑制潜力为0.118 µM。CDK9 /细胞周期蛋白T和Haspin的双重抑制可提供潜在的潜在抗有丝分裂剂，在进一步的抗癌研究中具有价值。

  DOI：

  10.1007/s00044-020-02560-1

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。
• 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.