5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carbonitrile | 1421581-12-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carbonitrile
• CAS: 1421581-12-5
• 化学式: C₁₆H₁₂ClN₅
• 分子量: 309.758
• InChiKey: NPKUNTFKYWHZGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  91.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carbonitrile 在 硫酸 、 水 、 三氟乙酸 作用下， 反应 8.0h， 以85%的产率得到5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide
  参考文献：
  名称：

  Pyrrole-3-carboxamides as potent and selective JAK2 inhibitors

  摘要：

  We report herein the discovery, structure guided design, synthesis and biological evaluation of a novel class of JAK2 inhibitors. Optimization of the series led to the identification of the potent and orally bioavailable JAK2 inhibitor 28 (NMS-P953). Compound 28 displayed significant tumour growth inhibition in SET-2 xenograft tumour model, with a mechanism of action confirmed in vivo by typical modulation of known biomarkers, and with a favourable pharmacokinetic and safety profile. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.06.025
• 作为产物：
  描述：

  5-氯-2-甲基-苯甲酸甲酯 在 aluminum (III) chloride 、 potassium 2-methylbutan-2-olate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 10.5h， 生成 5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carbonitrile
  参考文献：
  名称：

  Pyrrole-3-carboxamides as potent and selective JAK2 inhibitors

  摘要：

  We report herein the discovery, structure guided design, synthesis and biological evaluation of a novel class of JAK2 inhibitors. Optimization of the series led to the identification of the potent and orally bioavailable JAK2 inhibitor 28 (NMS-P953). Compound 28 displayed significant tumour growth inhibition in SET-2 xenograft tumour model, with a mechanism of action confirmed in vivo by typical modulation of known biomarkers, and with a favourable pharmacokinetic and safety profile. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.06.025

文献信息

• [EN] ALKYNYL SUBSTITUTED PYRIMIDINYL-PYRROLES ACTIVE AS KINASES INHIBITORS<br/>[FR] PYRIMIDINYL-PYRROLES SUBSTITUÉS ALCYNYLE AGISSANT COMME INHIBITEURS DE KINASE
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2013014039A1

  公开（公告）日：2013-01-31

  The present invention relates to alkynyl substituted pyrimidinyl-pyrrole compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular Jak and/or Src family kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such compounds or the pharmaceutical compositions containing them.

  本发明涉及烷基取代的嘧啶基吡咯烷化合物，可以调节蛋白激酶的活性，因此在治疗由失调的蛋白激酶活性引起的疾病方面具有用途，特别是Jak和/或Src家族激酶。本发明还提供了制备这些化合物的方法，包括这些化合物的药物组合物，以及利用这些化合物或含有它们的药物组合物治疗疾病的方法。
• ALKYNYL SUBSTITUTED PYRIMIDINYL-PYRROLES ACTIVE AS KINASES INHIBITORS
  申请人：Brasca Maria Gabriella

  公开号：US20140194406A1

  公开（公告）日：2014-07-10

  The present invention relates to alkynyl substituted pyrimidinyl-pyrrole compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular Jak and/or Src family kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such compounds or the pharmaceutical compositions containing them.

  本发明涉及烷基取代的嘧啶基-吡咯烷酮化合物，这些化合物可以调节蛋白激酶的活性，因此在治疗由蛋白激酶活性失调引起的疾病，特别是Jak和/或Src家族激酶方面具有用途。本发明还提供了制备这些化合物的方法，包括这些化合物的制药组合物，以及利用这些化合物或含有它们的制药组合物治疗疾病的方法。
• US8912200B2
  申请人：——

  公开号：US8912200B2

  公开（公告）日：2014-12-16
• Pyrrole-3-carboxamides as potent and selective JAK2 inhibitors
  作者：Maria Gabriella Brasca、Marcella Nesi、Nilla Avanzi、Dario Ballinari、Tiziano Bandiera、Jay Bertrand、Simona Bindi、Giulia Canevari、Davide Carenzi、Daniele Casero、Lucio Ceriani、Marina Ciomei、Alessandra Cirla、Maristella Colombo、Sabrina Cribioli、Cinzia Cristiani、Franco Della Vedova、Gabriele Fachin、Marina Fasolini、Eduard R. Felder、Arturo Galvani、Antonella Isacchi、Danilo Mirizzi、Ilaria Motto、Achille Panzeri、Enrico Pesenti、Paola Vianello、Paola Gnocchi、Daniele Donati

  DOI：10.1016/j.bmc.2014.06.025

  日期：2014.9

  We report herein the discovery, structure guided design, synthesis and biological evaluation of a novel class of JAK2 inhibitors. Optimization of the series led to the identification of the potent and orally bioavailable JAK2 inhibitor 28 (NMS-P953). Compound 28 displayed significant tumour growth inhibition in SET-2 xenograft tumour model, with a mechanism of action confirmed in vivo by typical modulation of known biomarkers, and with a favourable pharmacokinetic and safety profile. (C) 2014 Elsevier Ltd. All rights reserved.