5-(2-aminopyrimidin-4-yl)-2-(2-chloro-5-methylphenyl)-1H-pyrrole-3-carboxamide | 1403679-38-8

• 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-(2-chloro-5-methylphenyl)-1H-pyrrole-3-carboxamide
• CAS: 1403679-38-8
• 化学式: C₁₆H₁₄ClN₅O
• 分子量: 327.773
• InChiKey: MDONDWLCISBSBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(2-amino-pyrimidin-4-yl)-2-bromo-ethanone hydrobromide 在 bis-triphenylphosphine-palladium(II) chloride 、 HOBT*NH₃ 、 氢溴酸 、 sodium 、 sodium carbonate 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium chloride 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 25.0h， 生成 5-(2-aminopyrimidin-4-yl)-2-(2-chloro-5-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

文献信息

• [EN] SUBSTITUTED PYRIMIDINYL-PYRROLES ACTIVE AS KINASE INHIBITORS<br/>[FR] PYRIMIDINYLPYRROLES SUBSTITUÉS ACTIFS EN TANT QU'INHIBITEURS DE KINASES
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2012143248A1

  公开（公告）日：2012-10-26

  The present invention relates to substituted pyrimidinyl-pyrrole compounds of formula (I) which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular Janus 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.

  本发明涉及式(I)的取代嘧啶基-吡咯烷化合物，其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处，特别是Janus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。
• SUBSTITUTED PYRIMIDINYL-PYRROLES ACTIVE AS KINASE INHIBITORS
  申请人：Brasca Maria Gabriella

  公开号：US20140155421A1

  公开（公告）日：2014-06-05

  The present invention relates to substituted pyrimidinyl-pyrrole compounds of formula (I) which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular Janus 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.

  本发明涉及式（I）的取代嘧啶基-吡咯化合物，其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，特别是Janus激酶方面具有用处。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。
• US9283224B2
  申请人：——

  公开号：US9283224B2

  公开（公告）日：2016-03-15
• 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.