5-(2-amino-pyrimidin-4-yl)-2-(2,4-dichloro-phenyl)-1H-pyrrole-3-carboxylic acid amide

• 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-amino-pyrimidin-4-yl)-2-(2,4-dichloro-phenyl)-1H-pyrrole-3-carboxylic acid amide
• 英文别名: 5-(2-aminopyrimidin-4-yl)-2-(2,4-dichlorophenyl)-1H-pyrrole-3-carboxylic acid amide；Gemzar；5-(2-aminopyrimidin-4-yl)-2-(2,4-dichlorophenyl)-1H-pyrrole-3-carbonitrile；5-(2-aminopyrimidin-4-yl)-2-(2,4-dichlorophenyl)-1H-pyrrole-3-carboxamide
• 化学式: C₁₅H₁₁Cl₂N₅O
• 分子量: 348.191
• InChiKey: RKUKAACYUCUJEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(2-amino-pyrimidin-4-yl)-2-(2,4-dichloro-phenyl)-1H-pyrrole-3-carboxylic acid amide 、 顺丁烯二酸 以 甲醇 为溶剂， 生成 NMS-E354 maleate
  参考文献：
  名称：

  WO2011/57960

  摘要：

  公开号：
• 作为产物：
  描述：

  2,4-二氯苯甲酸 在 aluminum (III) chloride 水 、 sodium ethanolate 、 N,N'-羰基二咪唑 、 三氟乙酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 119.5h， 生成 5-(2-amino-pyrimidin-4-yl)-2-(2,4-dichloro-phenyl)-1H-pyrrole-3-carboxylic acid amide
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF 5-(2-AMINO-PYRIMIDIN-4-YL)-2-ARYL-1H-PYRROLE-3-CARBOXAMIDES
  [FR] PROCÉDÉ POUR L'ÉLABORATION DE 5-(2-AMINO-PYRIMIDIN-4-YL)-2-ARYL-1H-PYRROLE-3-CARBOXAMIDES

  摘要：

  该发明涉及一种制备5-(2-氨基嘧啶-4-基)-2-芳基-1H-吡咯-3-甲酰胺及其有用中间化合物的过程。该过程能够以高产率和纯度获得所需产品。合成从醚与β-酮酸酯的偶联开始；得到的化合物经乙酰化，然后与N,N-二甲基甲酰胺的二烷基醚反应，形成一个中间体，该中间体环化为5-(2-氨基嘧啶-4-基)-2-芳基-1H-吡咯-3-羧酸酯；然后羧酸酯被水解，生成的羧酸最终与适当形式的氨反应，得到所需的羧酰胺。根据该发明的方法制备的化合物具有蛋白激酶抑制活性，更具体地说，具有Cdc7或Cdc7/Cdks抑制活性。这些化合物在治疗各种癌症、细胞增殖紊乱以及与蛋白激酶相关的疾病方面具有用处。

  公开号：

  WO2011054714A1

文献信息

• [EN] PROCESS FOR THE PREPARATION OF 5-(2-AMINO-PYRIMIDIN-4-YL)-2-ARYL-1H-PYRROLE-3-CARBOXAMIDES<br/>[FR] PROCÉDÉ POUR L'ÉLABORATION DE 5-(2-AMINO-PYRIMIDIN-4-YL)-2-ARYL-1H-PYRROLE-3-CARBOXAMIDES
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2011054714A1

  公开（公告）日：2011-05-12

  The invention relates to a process for the preparation of 5-(2-amino-pyrimidin-4-yl)-2-aryl-1H-pyrrole-3- carboxamides and to the useful intermediate compounds of such process. The process allows to obtain the desired products in high yields and purity. The synthesis is starting from the coupling of an acetal with a beta-ketoester; the resultant compound is acetylated and then reacted with a dialkyl acetal of N,N-dimethylformamide to give an intermediate which is cyclized to 5-(2-amino-pyrimidin-4-yl)-2-aryl-1H-pyrrole-3-carboxylic ester; the carboxylic ester is then hydrolyzed and the resultant carboxylic acid is finally condensed with an appropriate form of ammonia to give the desired carboxamide. The compounds prepared according to the process of the invention are endowed with protein kinase inhibiting activity and, more particularly, Cdc7 or Cdc7/Cdks inhibiting activity. The compounds are useful in the treatment of a variety of cancers, cell proliferative disorders and diseases associated with protein kinases.

  该发明涉及一种制备5-(2-氨基嘧啶-4-基)-2-芳基-1H-吡咯-3-甲酰胺及其有用中间化合物的过程。该过程能够以高产率和纯度获得所需产品。合成从醚与β-酮酸酯的偶联开始；得到的化合物经乙酰化，然后与N,N-二甲基甲酰胺的二烷基醚反应，形成一个中间体，该中间体环化为5-(2-氨基嘧啶-4-基)-2-芳基-1H-吡咯-3-羧酸酯；然后羧酸酯被水解，生成的羧酸最终与适当形式的氨反应，得到所需的羧酰胺。根据该发明的方法制备的化合物具有蛋白激酶抑制活性，更具体地说，具有Cdc7或Cdc7/Cdks抑制活性。这些化合物在治疗各种癌症、细胞增殖紊乱以及与蛋白激酶相关的疾病方面具有用处。
• [EN] PROCESS FOR THE PREPARATION OF 5-(2-AMINO-PYRIMIDIN-4-YL)-2-ARYL-1H-PYRROLE-3-CARBOXAMIDES<br/>[FR] PROCÉDÉ DE PRÉPARATION DE 5-(2-AMINO- PYRIMIDIN-4-YL)-2-ARYL-LH-PYRROLE-3-CARBOXAMIDES
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2009133170A1

  公开（公告）日：2009-11-05

  The present invention relates to a process for the preparation of 5-(2-amino- pyrimidin-4-yl)-2-aryl-lH-pyrrole-3-carboxamides and to the useful intermediate compounds of such process. 5-(2-Amino-pyrimidin-4-yl)-2-aryl-lH-pyrrole-3-carboxamides are described and claimed in WO2007110344, which also discloses processes for their preparation. These compounds can be advantageously prepared through a process which allows to obtain the desired products in high yields and purity and with a limited number of steps. The synthesis is starting from a cyano pyrrole derivative, and is characterized from the final hydrolysis of 5-(2-amino-pyrimidin-4-yl)-2-aryl-lH-pyrrole-3- carbonitrile. The compounds prepared according to the process of the present invention are endowed with protein kinase inhibiting activity and, more particularly, Cdc7 or Cdc7/Cdks inhibiting activity. The compounds are therefore useful in the treatment of a variety of cancers, cell proliferative disorders and diseases associated with protein kinases.

  本发明涉及一种制备5-(2-氨基嘧啶-4-基)-2-芳基-1H-吡咯-3-羧酰胺的方法，以及该过程中有用的中间化合物。在WO2007110344中描述并声明了5-(2-氨基嘧啶-4-基)-2-芳基-1H-吡咯-3-羧酰胺，并且还揭示了它们的制备方法。这些化合物可以通过一种允许以高收率和纯度，并且步骤有限的方法制备得到。该合成是从一个氰基吡咯衍生物开始的，并且其特点在于最终水解5-(2-氨基嘧啶-4-基)-2-芳基-1H-吡咯-3-羰基腈。根据本发明的方法制备的化合物具有蛋白激酶抑制活性，更具体地说，是Cdc7或Cdc7/Cdks抑制活性。因此，这些化合物在治疗各种癌症、细胞增殖性疾病和与蛋白激酶相关的疾病方面是有用的。
• 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。
• PYRIDYL-AND PYRIMIDINYL-SUBSTITUTED PYRROLE-, THIOPHENE- AND FURANE-DERIVATIVES AS KINASE INHIBITORS
  申请人：NERVIANO MEDICAL SCIENCES S.R.L.

  公开号：US20150051237A1

  公开（公告）日：2015-02-19

  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.

  本发明提供了式（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式（I）的化合物的方法和中间体，包括它们的制药组合物和治疗细胞增殖性疾病的方法。事实上，式（I）的化合物在治疗与蛋白激酶活性失调相关的疾病，如癌症中是有用的。
• ANTICANCER AGENT COMPOSITION
  申请人：Carna Biosciences, Inc.

  公开号：EP3100742A1

  公开（公告）日：2016-12-07

  Provided is a pharmaceutical composition comprising a Cdc7 inhibitor and an M phase promoter. In particular, the Cdc7 inhibitor contained in the pharmaceutical composition is a furanone derivative represented by formula (I), or a pharmaceutically acceptable salt thereof. (In the formula, A is -COOR1 or a hydrogen atom; R1 is a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocycle; R2 and R3 are the same or different and are each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted phenyl group, an optionally substituted heterocycle, an optionally substituted heterocyclic condensed ring, or an optionally substituted amino group. Alternatively, R2 and R3 may, together with the nitrogen atoms bonding the same, form an optionally substituted heterocycle or optionally substituted heterocyclic condensed ring. R4 is a hydrogen atom or halogen atom. However, if A is -COOR1, R2 and R3 are not both simultaneously optionally substituted amino groups. When A is a hydrogen atom, R3 is a hydrogen atom.)

  本发明提供了一种药物组合物，其中包含一种 Cdc7 抑制剂和一种 M 期促进剂。特别是，药物组合物中所含的 Cdc7 抑制剂是由式（I）表示的呋喃酮衍生物或其药学上可接受的盐。(式中，A为-COOR1或氢原子；R1为氢原子、任选取代的烃基或任选取代的杂环；R2和R3相同或不同，各自为氢原子、任选取代的烃基、任选取代的苯基、任选取代的杂环、任选取代的杂环缩合环或任选取代的氨基。或者，R2 和 R3 可与结合在一起的氮原子一起形成任选取代的杂环或任选取代的杂环缩合环。R4 是氢原子或卤素原子。但是，如果 A 是-COOR1，R2 和 R3 不能同时是任选取代的氨基。当 A 为氢原子时，R3 为氢原子）。