6-(4-吡啶基)-2-喹唑啉胺 | 1008505-37-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 6-(4-吡啶基)-2-喹唑啉胺
• 中文别名: 6-(4-吡啶)-2-喹唑啉胺
• 英文名称: 6-pyridin-4-ylquinazolin-2-amine
• 英文别名: 6-(Pyridin-4-yl)quinazolin-2-amine
• CAS: 1008505-37-0
• 化学式: C₁₃H₁₀N₄
• 分子量: 222.249
• InChiKey: XDULIFZWNIEGCE-UHFFFAOYSA-N

物化性质

• 沸点：
  477.6±37.0 °C(Predicted)
• 密度：
  1.301

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(4-吡啶基)-2-喹唑啉胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium cyanoborohydride 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 3.0h， 生成 N-(4-{[(2-methoxyethyl)amino]methyl}phenyl)-6-pyridin-4-ylquinazolin-2-amine
  参考文献：
  名称：

  Discovery and Optimization of a Novel Series of Potent Mutant B-Raf^V600E Selective Kinase Inhibitors

  摘要：

  B-Raf represents an attractive target for anticancer therapy and the development of small molecule B-Raf inhibitors has delivered new therapies for metastatic melanoma patients. We have discovered a novel class of small molecules that inhibit mutant B-Raf(V600E) kinase activity both in vitro and in vivo. Investigations into the structure-activity relationships of the series are presented along with efforts to improve upon the cellular potency, solubility, and phannacokinetic profile. Compounds selectively inhibited B-Raf(V600E) in vitro and showed preferential antiproliferative activity in mutant B-Raf(V600E) cell lines and exhibited selectivity in a kinase panel against other kinases. Examples from this series inhibit growth of a B-Raf(V600E) A375 xenograft in vivo at a well-tolerated dose. In addition, aminoquinazolines described herein were shown to display pERK elevation in nonmutant B-Raf cell lines in vitro.

  DOI：

  10.1021/jm301658d
• 作为产物：
  描述：

  5-溴-2-氟苯甲醛 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 17.0h， 生成 6-(4-吡啶基)-2-喹唑啉胺
  参考文献：
  名称：

  Discovery and Optimization of a Novel Series of Potent Mutant B-Raf^V600E Selective Kinase Inhibitors

  摘要：

  B-Raf represents an attractive target for anticancer therapy and the development of small molecule B-Raf inhibitors has delivered new therapies for metastatic melanoma patients. We have discovered a novel class of small molecules that inhibit mutant B-Raf(V600E) kinase activity both in vitro and in vivo. Investigations into the structure-activity relationships of the series are presented along with efforts to improve upon the cellular potency, solubility, and phannacokinetic profile. Compounds selectively inhibited B-Raf(V600E) in vitro and showed preferential antiproliferative activity in mutant B-Raf(V600E) cell lines and exhibited selectivity in a kinase panel against other kinases. Examples from this series inhibit growth of a B-Raf(V600E) A375 xenograft in vivo at a well-tolerated dose. In addition, aminoquinazolines described herein were shown to display pERK elevation in nonmutant B-Raf cell lines in vitro.

  DOI：

  10.1021/jm301658d

文献信息

• PYRIDINYLQUINAZOLINAMINE DERIVATIVES AND THEIR USE AS B-RAF INHIBITORS
  申请人：Aquila Brian

  公开号：US20100216791A1

  公开（公告）日：2010-08-26

  The invention relates to chemical compounds of the formula (I) or pharmaceutically acceptable salts thereof, which possess B-Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.

  本发明涉及化学式（I）的化合物或其药学上可接受的盐，其具有B-Raf抑制活性，因此在抗癌活性和人或动物体的治疗方法中有用。本发明还涉及制造所述化学化合物的过程，包含它们的制药组合物以及它们在制造用于产生温血动物（例如人）中的抗癌效应的药物中的使用。
• WO2008/20203
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] PYRIDINYLQUINAZ0LINAMINE DERIVATIVES AND THEIR USE AS B-RAF INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIDINYLQUINAZOLINAMINE ET LEUR UTILISATION COMME INHIBITEURS DE B-RAF
  申请人：ASTRAZENECA AB

  公开号：WO2008020203A1

  公开（公告）日：2008-02-21

  [EN] The invention relates to chemical compounds of the formula (I) or pharmaceutically acceptable salts thereof, which possess B-Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
  [FR] L'invention concerne des composés chimiques représentés par la formule (I) ou les sels pharmaceutiquement acceptables de ses composés, lesquels possèdent une activité inhibitrice de B-Raf et sont, en conséquence, utiles pour leur activité anti-cancer et, de ce fait, dans des procédés thérapeutiques chez l'humain ou l'animal. L'invention porte également sur des procédés de fabrication desdits composés chimiques, sur des compositions pharmaceutiques contenant lesdits composés chimiques et sur leur utilisation dans la fabrication de médicaments destinés à produire un effet anti-cancer chez un animal à sang chaud tel que l'homme.
• Discovery and Optimization of a Novel Series of Potent Mutant B-Raf^V600E Selective Kinase Inhibitors
  作者：Melissa M. Vasbinder、Brian Aquila、Martin Augustin、Huawei Chen、Tony Cheung、Donald Cook、Lisa Drew、Benjamin P. Fauber、Steve Glossop、Michael Grondine、Edward Hennessy、Jeffrey Johannes、Stephen Lee、Paul Lyne、Mario Mörtl、Charles Omer、Sangeetha Palakurthi、Timothy Pontz、Jon Read、Li Sha、Minhui Shen、Stefan Steinbacher、Haixia Wang、Allan Wu、Minwei Ye

  DOI：10.1021/jm301658d

  日期：2013.3.14

  B-Raf represents an attractive target for anticancer therapy and the development of small molecule B-Raf inhibitors has delivered new therapies for metastatic melanoma patients. We have discovered a novel class of small molecules that inhibit mutant B-Raf(V600E) kinase activity both in vitro and in vivo. Investigations into the structure-activity relationships of the series are presented along with efforts to improve upon the cellular potency, solubility, and phannacokinetic profile. Compounds selectively inhibited B-Raf(V600E) in vitro and showed preferential antiproliferative activity in mutant B-Raf(V600E) cell lines and exhibited selectivity in a kinase panel against other kinases. Examples from this series inhibit growth of a B-Raf(V600E) A375 xenograft in vivo at a well-tolerated dose. In addition, aminoquinazolines described herein were shown to display pERK elevation in nonmutant B-Raf cell lines in vitro.