ethyl 4-(2-aminopyrimidin-4-yl)-2-cyano-4-oxobutanoate | 951784-50-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: ethyl 4-(2-aminopyrimidin-4-yl)-2-cyano-4-oxobutanoate
• 英文别名: 4-(2-amino-pyrimidin-4-yl)-2-cyano-4-oxo-butyric acid ethyl ester
• CAS: 951784-50-2
• 化学式: C₁₁H₁₂N₄O₃
• 分子量: 248.241
• InChiKey: ANPQCMZHBAMTRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 4-(2-aminopyrimidin-4-yl)-2-cyano-4-oxobutanoate 在 bis-triphenylphosphine-palladium(II) chloride 、 氢溴酸 、 sodium carbonate 、 溶剂黄146 、 lithium chloride 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 25.0h， 生成 5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-methyl-phenyl)-1H-pyrrole-3-carboxylic acid
  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：

  氰乙酸乙酯 在 乙醇 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 ethyl 4-(2-aminopyrimidin-4-yl)-2-cyano-4-oxobutanoate
  参考文献：
  名称：

  WO2007/110344

  摘要：

  公开号：

文献信息

• Cdc7 Kinase Inhibitors: 5-Heteroaryl-3-Carboxamido-2-Aryl Pyrroles as Potential Antitumor Agents. 1. Lead Finding
  作者：Maria Menichincheri、Clara Albanese、Cristina Alli、Dario Ballinari、Alberto Bargiotti、Marina Caldarelli、Antonella Ciavolella、Alessandra Cirla、Maristella Colombo、Francesco Colotta、Valter Croci、Roberto D’Alessio、Matteo D’Anello、Antonella Ermoli、Francesco Fiorentini、Barbara Forte、Arturo Galvani、Patrizia Giordano、Antonella Isacchi、Katia Martina、Antonio Molinari、Jürgen K. Moll、Alessia Montagnoli、Paolo Orsini、Fabrizio Orzi、Enrico Pesenti、Antonio Pillan、Fulvia Roletto、Alessandra Scolaro、Marco Tatò、Marcellino Tibolla、Barbara Valsasina、Mario Varasi、Paola Vianello、Daniele Volpi、Corrado Santocanale、Ermes Vanotti

  DOI：10.1021/jm100504d

  日期：2010.10.28

  we report on a new chemical class of 5-heteroaryl-3-carboxamido-2-substituted pyrroles (1A) that offers advantages of chemistry diversification and synthetic simplification. This work led to the identification of compound 18, with biochemical data and ADME profile similar to those of compound 1 but characterized by superior efficacy in an in vivo model. Derivative 18 represents a new lead compound worthy

  Cdc7丝氨酸/苏氨酸激酶是真核生物中DNA合成的关键调节剂。通过si RNA或原型小分子对Cdc7的抑制在肿瘤细胞中引起p53独立凋亡，同时可逆地阻止初级成纤维细胞的细胞周期进程。这暗示着Cdc7激酶可以被认为是抗癌治疗的潜在靶标。我们先前曾报道吡咯并吡啶并酮（例如1）是Cdc7激酶的有效和选择性抑制剂，具有良好的细胞效力和体外ADME特性，但药代动力学不理想。在这里我们报告了一种新的化学类别的5-杂芳基-3-羧酰胺基-2-取代的吡咯（1A）具有化学多样化和合成简化的优势。这项工作导致了化合物18的鉴定，其生化数据和ADME谱与化合物1相似，但在体内模型中具有优越的功效。衍生物18代表一种新的先导化合物，值得进一步研究，以最终确定出临床候选药物。
• [EN] SUBSTITUTED PYRROLO-PYRIMIDINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE PYRROLOPYRIMIDINE SUBSTITUÉS, LEUR PROCÉDÉ DE PRÉPARATION ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2009040399A1

  公开（公告）日：2009-04-02

  Substituted pyrrolo-pyrimidine derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a dysregulated protein kinase activity, like cancer.

  公开了公式（I）的取代吡咯-嘧啶衍生物及其药用盐，如规范中定义的，以及它们的制备方法和包含它们的药物组合物；本发明的化合物可能在治疗与蛋白激酶活性失调相关的疾病，如癌症中有用。
• PYRIDYL-AND PYRIMIDINYL-SUBSTITUTED PYRROLE-, THIOPHENE-AND FURANE-DERIVATIVES AS KINASE INHIBITORS
  申请人：Vanotti Ermes

  公开号：US20090099221A1

  公开（公告）日：2009-04-16

  The present invention provides compounds of the formula (I), or the pharmaceutically acceptable salts thereof, wherein G, W, R 2 , R 3 , R 4 , R 5 and R 6 are as defined in the specification. Further objects of the invention are processes and intermediates for the preparation of the compounds of the formula (I), pharmaceutical compositions comprising them and methods for treating cell proliferative disorders. As a matter of fact, the compounds of the formula (I) are useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer

  本发明提供公式（I）的化合物或其药学上可接受的盐，其中G、W、R2、R3、R4、R5和R6如规范中所定义。本发明的进一步目的是制备公式（I）化合物的过程和中间体，包括它们的制药组合物以及治疗细胞增殖性疾病的方法。事实上，公式（I）的化合物在治疗与蛋白激酶活性不规则相关的疾病，如癌症方面具有用途。
• Substituted Pyrrolo-Pyrimidine Derivatives, Process for Their Preparation and Their Use as Kinase Inhibitors
  申请人：Caruso Michele

  公开号：US20120122882A1

  公开（公告）日：2012-05-17

  Substituted pyrrolo-pyrimidine derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a dysregulated protein kinase activity, like cancer.

  本文披露了公式(I)的取代嘧啶-吡咯衍生物及其药学上可接受的盐，以及其制备方法和包含它们的制药组合物；本发明的化合物可能在治疗与蛋白激酶活性失调相关的疾病，如癌症方面具有用途。
• Substituted pyrrolo-pyrimidine derivatives, process for their preparation and their use as kinase inhibitors
  申请人：Caruso Michele

  公开号：US08426417B2

  公开（公告）日：2013-04-23

  Substituted pyrrolo-pyrimidine derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a dysregulated protein kinase activity, like cancer.

  本发明公开了公式（I）的替代吡咯-嘧啶衍生物及其药学上可接受的盐，其定义在说明书中，以及制备它们的过程和包含它们的制药组合物；本发明的化合物可能在治疗与蛋白激酶活性失调相关的疾病（如癌症）中有用。