5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-N-(2-hydroxyethyl)-1H-pyrrole-3-carboxamide | 1403679-53-7

• 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)-N-(2-hydroxyethyl)-1H-pyrrole-3-carboxamide
• CAS: 1403679-53-7
• 化学式: C₁₈H₁₈ClN₅O₂
• 分子量: 371.826
• InChiKey: ZXKPOMXJHLXQKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  5

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 、 氢溴酸 、 sodium 、 sodium carbonate 、 1-羟基苯并三唑 、 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-(5-chloro-2-methylphenyl)-N-(2-hydroxyethyl)-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

• BIARYL DERIVATIVES AS NACHR MODULATORS
  申请人：Sinha Neelima

  公开号：US20140155433A1

  公开（公告）日：2014-06-05

  Disclosed is a compound of formula (I): wherein ‘D’, ‘E’, ‘m’, ‘n’ and R 1 -R 4 are as described herein, as a modulator of nicotinic acetylcholine receptors particularly the α7 subtype, in a subject in need thereof, as well as analogues, prodrugs, isotopically substituted analogs, metabolites, pharmaceutically acceptable salts, polymorphs, solvates, isomers, clathrates, and co-crystal thereof, for use either alone or in combinations with suitable other medicaments, and pharmaceutical compositions containing such compounds and analogues. Also disclosed are a process of preparation of the compounds and the intended uses thereof in therapy, particularly in the prophylaxis and therapy of disorders such as Alzheimer's disease, mild cognitive impairment, senile dementia, and the like.

  本发明涉及一种式(I)的化合物：其中，‘D’，‘E’，‘m’，‘n’和R1-R4如此描述，作为尼古丁乙酰胆碱受体的调节剂，特别是α7亚型，在需要的受体中使用，以及类似物，前药，同位素替代物，代谢物，药学上可接受的盐，多晶形，溶剂化物，异构体，包合物和共晶体，单独或与适当的其他药物组合使用的用途，以及含有这些化合物和类似物的药物组合物。还公开了制备这些化合物的过程及其在治疗中的预期用途，特别是在防治阿尔茨海默病，轻度认知障碍，老年性痴呆等疾病方面的应用。
• 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。
• US8946432B2
  申请人：——

  公开号：US8946432B2

  公开（公告）日：2015-02-03
• 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.