4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine | 341998-55-8

• 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-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
• 英文别名: Meriolin 1
• CAS: 341998-55-8
• 化学式: C₁₁H₉N₅
• 分子量: 211.226
• InChiKey: HQHSJJZIICGOIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.5
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  4-三氟甲基苯磺酰氯 、 4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以77%的产率得到4-(1-((4-(trifluoromethyl)phenyl)sulfonyl)-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：

  7-氮杂吲哚 在 甲醇 、 四(三苯基膦)钯 、 碘 、 caesium carbonate 、 三乙胺 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.67h， 生成 4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine
  参考文献：
  名称：

  新型美林素衍生物作为快速的细胞凋亡诱导剂。

  摘要：

  具有多激酶抑制剂活性的3-（杂）芳基取代的7-氮杂吲哚可通过一锅增田（Masuda）硼酸酯化-铃木偶联序列容易地获得。几种有前途的衍生物被确定为凋亡诱导剂，并强调了多激酶的抑制潜力，为鞘氨醇激酶2抑制剂。我们的测量结果提供了对美丽素衍生物的结构-活性关系的更多见解，表明带有吡啶部分带有2位氨基的吡啶部分的衍生物是最有活性的抗癌化合物，因此是未来体内研究的极有希望的候选者。

  DOI：

  10.1016/j.bmc.2019.06.029

文献信息

• Rapid synthesis of bis(hetero)aryls by one-pot Masuda borylation–Suzuki coupling sequence and its application to concise total syntheses of meridianins A and G
  作者：Eugen Merkul、Elisabeth Schäfer、Thomas J. J. Müller

  DOI：10.1039/c1ob05310h

  日期：——

  3-(Hetero)aryl substituted indoles, 7-azaindoles, and pyrroles can be obtained in a very concise fashion via a one-pot Masuda borylation–Suzuki coupling sequence. The concise total syntheses of the marine natural products meridianins A (5) and G (4i) nicely illustrate the utility of this methodology.

  通过一锅增田（Masuda）硼酸酯化-铃木（Suzuki）偶联序列可以非常简明的方式获得3-（杂）芳基取代的吲哚，7-氮杂吲哚和吡咯。海洋天然产物子午线素A（5）和G（4i）的简洁的总合成很好地说明了该方法的实用性。
• Metal free C–H functionalization of diazines and related heteroarenes with organoboron species and its application in the synthesis of a CDK inhibitor, meriolin 1
  作者：Thanusha Thatikonda、Umed Singh、Srinivas Ambala、Ram A. Vishwakarma、Parvinder Pal Singh

  DOI：10.1039/c6ob00526h

  日期：——

  Here, we report a metal-free cross-coupling reaction of diazines and related heteroarenes with organoboron species.

  在这里，我们报告二嗪和相关杂芳烃与有机硼物种的无金属交叉偶联反应。
• PYRROLO[2,3-B]PYRIDINE COMPOUNDS, AZAINDOLE COMPOUNDS USED FOR SYNTHESIZING SAID PYRROLO[2,3-B]PYRIDINE COMPOUNDS, METHODS FOR THE PRODUCTION THEREOF, AND USES THEREOF
  申请人：Meijer Laurent

  公开号：US20100184790A1

  公开（公告）日：2010-07-22

  The invention relates to pyrrolo[2,3-b]pyridine compounds and azaindole compounds used for the synthesis thereof. The invention also relates to methods for the production thereof and the uses thereof. Said novel pyrrolo[2,3-b]pyridine compounds according to the invention have great antiproliferative, apoptotic, and neuroprotective activities. The invention particularly applies to the pharmaceutical field.

  该发明涉及用于合成吡咯并[2,3-b]吡啶化合物和氮杂吲哚化合物的方法。该发明还涉及其生产方法和用途。根据该发明，所述新型吡咯并[2,3-b]吡啶化合物具有很强的抗增殖、凋亡和神经保护活性。该发明特别适用于药物领域。
• Azaindoles useful as inhibitors of JAK and other protein kinases
  申请人：Salituro Francesco

  公开号：US20070043063A1

  公开（公告）日：2007-02-22

  The present invention relates to 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.

  本发明涉及蛋白激酶抑制剂。本发明还提供包含本发明化合物的药物组合物以及使用这些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：Salituro Francesco

  公开号：US20120258958A1

  公开（公告）日：2012-10-11

  The present invention relates to 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.

  本发明涉及蛋白激酶抑制剂。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。