N-[3-(1H-imidazol-1-yl)phenyl]-4-(3-pyridinyl)-2-pyrimidinamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-[3-(1H-imidazol-1-yl)phenyl]-4-(3-pyridinyl)-2-pyrimidinamine
• 英文别名: N-(3-<1-imidazolyl>-phenyl)-4-(3-pyridyl)-2-pyrimidinamine；N-(3-1H-imidazol-1-ylphenyl)-4-(pyridin-3-yl)-2-pyrimidinamine；N-(3-1H-imidazol-1-ylphenyl)-4-(3-pyridyl)-2-pyrimidinamine；(3-Imidazol-1-yl-phenyl)-(4-pyridin-3-yl-pyrimidin-2-yl)-amine；N-(3-imidazol-1-ylphenyl)-4-pyridin-3-ylpyrimidin-2-amine
• 化学式: C₁₈H₁₄N₆
• 分子量: 314.349
• InChiKey: IDWXVEDTQPGXCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  间氟硝基苯 在 platinum(IV) oxide 氢气 、 potassium carbonate 作用下， 以 乙醇 、 乙二醇甲醚 、 二甲基亚砜 为溶剂， 反应 50.5h， 生成 N-[3-(1H-imidazol-1-yl)phenyl]-4-(3-pyridinyl)-2-pyrimidinamine
  参考文献：
  名称：

  Preparation of substituted N-phenyl-4-aryl-2-pyrimidinamines as mediator release inhibitors

  摘要：

  The role of immunologically released mediators, such as histamine, leukotrienes, and platelet-activating factor, is well-established for asthma and other allergic disorders. Developing therapeutic agents which would block mediator release from mast cells and other relevant cell types would provide a rational approach to asthma therapy. Using human basophil as a screen, a series of 4-aryl-2-(phenylamino)pyrimidines was found which inhibited mediator release. These compounds were prepared by condensing acetyl heterocycles with dimethylformamide dimethyl acetal to form enaminones which are cyclized with aryl guanidines to give pyrimidines. After examining a large number of analogs, N-[3-(1H-imidazol-1-yl)phenyl]-4-(2-pyridinyl)-2-pyrimidinamine (1-27) was chosen for toxicological evaluation.

  DOI：

  10.1021/jm00071a002

文献信息

• Process for the synthesis of
  申请人：American Cyanamid Company

  公开号：US05064963A1

  公开（公告）日：1991-11-12

  The invention provides a novel process for producing N-[3-(1H-imidazol-1-yl)phenyl]-4-(substituted)-2 pyrimidinamine compounds in which the substituent is a 2-pyridinyl, 3-pyrindinyl, 4-pyridinyl, 2-furanyl or 2-thienyl group. The process includes the steps of (1) reacting a 3-(1H-imidazol-1-yl)benzamine with cyanamide and a halogen acid while controlling the pH of the reaction between pH about 2 to abourt 3.5 and recovering a [3-(1H-imidazol-1-yl)phenyl] guanidine dihydrohalide and (2) reacting the [3-(1H-imidazol-1-yl)phenyl] guanidine dihydrohalide so recovered with an appropriately substituted 3-dimethylamino-1-(substituted)-2-propen-1-one and a base at a pH of from about 10.5 to about 11.5 and recovering the N-[3-(1H-imidazol-1-yl)phenyl-4-(substituted)-2-pyrimidamine compound so produced. The novel process provides improved yield and purity by adhering to the stated crucial pH ranges.

  该发明提供了一种新型的生产N-[3-(1H-咪唑-1-基)苯基]-4-(取代基)-2-嘧啶胺化合物的方法，其中取代基是2-吡啶基、3-吡啶基、4-吡啶基、2-呋喃基或2-噻吩基。该方法包括以下步骤：(1)在控制反应的pH在约2到约3.5之间的条件下，将3-(1H-咪唑-1-基)苯胺与氰胺和一种卤酸反应，从中回收[3-(1H-咪唑-1-基)苯基]胍二氢卤化物；(2)将回收的[3-(1H-咪唑-1-基)苯基]胍二氢卤化物与适当取代的3-二甲胺基-1-(取代基)-2-丙烯-1-酮和碱在pH约为10.5到约11.5的条件下反应，从中回收所生产的N-[3-(1H-咪唑-1-基)苯基]-4-(取代基)-2-嘧啶胺化合物。这种新型方法通过遵循所述关键的pH范围提高了产量和纯度。
• Improved process for the synthesis of N-3-(1H-imidazol-1-yl)phenyl-4-(substituted)-2-pyrimidinamines
  申请人：AMERICAN CYANAMID COMPANY

  公开号：EP0453731A2

  公开（公告）日：1991-10-30

  The invention provides a novel process for producing N-[3-(1H-imidazol-1-yl-4-(substituted-2-pyrimidinamine compounds in which the substituent is a 2-pyridinyl, 3-pyrindinyl, 4-pyridinyl, 2-furanyl or 2-thienyl group. The process includes the steps of (1) reacting a 3-(1H-imidazol-1-yl)benzamine with cyanamide and a halogen acid while controlling the pH of the reaction between pH about 2 to about 3.5 and recovering a [3-(1H-imidazol-1-yl)phenyl] guanidine dihydrohalide and (2) reacting the [3-(1H-imidazol-1-yl)phenyl] quanidine dihydrohalide so recovered with an appropriately substituted 3-dimethylamino-1-(substituted)-2-propen-1-one and a base at a pH of from about 10.5 to about 11.5 and recovering the N-[3-(1H-imidazol-1-yl)phenyl-4-(substituted)-2-pyrimidamine compound so produced. The novel process provides improved yield and purity by adhering to the stated crucial pH ranges.

  本发明提供了一种生产N-[3-(1H-咪唑-1-基-4-(取代-2-嘧啶胺化合物，其中取代基为2-吡啶基、3-吡啶基、4-吡啶基、2-呋喃基或2-噻吩基]的新工艺。该工艺包括以下步骤：(1)将 3-(1H-咪唑-1-基)苯胺与氰酰胺和卤素酸反应，同时将反应的 pH 值控制在约 2 至约 3.(2) 将回收的[3-(1H-咪唑-1-基)苯基]胍二氢卤化物与适当取代的 3-二甲氨基-1-(取代)-2-丙烯-1-酮和碱在 pH 值约为 10.5至约11.5的pH值下，用适当取代的3-二甲基氨基-1-(取代)-2-丙烯-1-酮和碱回收生成的N-[3-(1H-咪唑-1-基)苯基-4-(取代)-2-嘧啶胺化合物。这种新工艺通过遵守所述的关键 pH 值范围，提高了产率和纯度。
• Verwendung von Pyrimidinderivaten als Proteinkinase C-Inhibitoren und Antitumormittel
  申请人：CIBA-GEIGY AG

  公开号：EP0588762A1

  公开（公告）日：1994-03-23

  Die Erfindung betrifft die Verwendung bekannter N-Phenyl-2-pyrimidinamin-derivate der Formel I zur Hemmung der Proteinkinase C in Warmblütern, d.h. z.B. als Antitumormittel. Die Substituenten in Formel I haben die in Anspruch 1 angegebenen Bedeutungen.

  本发明涉及式 I 的已知 N-苯基-2-嘧啶胺衍生物在温血动物中抑制蛋白激酶 C 的用途，即用作抗肿瘤药物等。 式 I 中的取代基具有权利要求 1 中给出的含义。
• Potent and selective inhibitors of the Abl-kinase: phenylamino-pyrimidine (PAP) derivatives
  作者：Jürg Zimmermann、Elisabeth Buchdunger、Helmut Mett、Thomas Meyer、Nicholas B. Lydon

  DOI：10.1016/s0960-894x(96)00601-4

  日期：1997.1

  Due to its relatively clear etiology, Chronic myelogenous leukemia (CML) represents an ideal disease target for a therapy using a selective inhibitor of the Bcr-Abl tyrosine protein kinase. Extensive optimization of the class of phenylamino-pyrimidines yielded highly potent and selective Bcr-Abl kinase inhibitors. Compound 1 shows high potency (IC50 = 38 nM) and selectivity for the Abl tyrosine protein kinase at the in vitro level. (C) 1997, Elsevier Science Ltd.
• TORLEY, LAWRENCE W.;JOHNSON, BERNARD D.;DUSZA, JOHN P.
  作者：TORLEY, LAWRENCE W.、JOHNSON, BERNARD D.、DUSZA, JOHN P.

  DOI：——

  日期：——