6-(4-methylpyridin-3-yl)quinazolin-2-amine | 882679-91-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-(4-methylpyridin-3-yl)quinazolin-2-amine
• CAS: 882679-91-6
• 化学式: C₁₄H₁₂N₄
• 分子量: 236.276
• InChiKey: RTMODEDXYWMCGB-UHFFFAOYSA-N

物化性质

• 沸点：
  480.3±37.0 °C(Predicted)
• 密度：
  1.263±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 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-methylpyridin-3-yl)quinazolin-2-amine 、 对溴苯甲醛 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以73%的产率得到4-{[6-(4-methylpyridin-3-yl)quinazolin-2-yl]amino}benzaldehyde
  参考文献：
  名称：

  WO2008/68507

  摘要：

  公开号：
• 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-methylpyridin-3-yl)quinazolin-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

文献信息

• Aryl nitrogen-containing bicyclic compounds and methods of use
  申请人：Patel F. Vinod

  公开号：US20070054916A1

  公开（公告）日：2007-03-08

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , A 3 , B, R 1 , R 2 , R 3 and R 4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

  这项发明涉及一类新的化合物，用于预防和治疗蛋白激酶介导的疾病，包括炎症、癌症和相关疾病。这些化合物具有一般的化学式I，其中A1、A2、A3、B、R1、R2、R3和R4在此有定义。因此，该发明还涉及包括该发明的化合物的药物组合物，使用该发明的化合物和组合物预防和治疗激酶介导的疾病的方法，以及用于制备该发明的化合物的中间体和方法。
• ARYL NITROGEN-CONTAINING BICYCLIC COMPOUNDS AND THEIR USE AS KINASE INHIBITORS
  申请人：AMGEN INC.

  公开号：EP1836174A2

  公开（公告）日：2007-09-26
• [EN] ARYL NITROGEN-CONTAINING BICYCLIC COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSES BICYCLIQUES AZOTES D'ARYLE ET LEURS PROCEDES D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2006039718A2

  公开（公告）日：2006-04-13

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I, wherein A1, A2, A3, B, R1, R2, R3 and R4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.
• [EN] CHEMICAL COMPOUNDS-576<br/>[FR] COMPOSÉS CHIMIQUES 576
  申请人：ASTRAZENECA AB

  公开号：WO2008068507A2

  公开（公告）日：2008-06-12

  [EN] The invention relates to chemical compounds of the formula (I): or pharmaceutically 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 de formule (I) : ou des sels acceptables du point de vue pharmaceutique de ceux-ci, lesquels possèdent une activité d'inhibition du B-Raf et sont par conséquent utiles pour leur activité anticancéreuse et donc dans des procédés de traitement du corps de l'homme ou de l'animal. L'invention concerne également des procédés pour la fabrication desdits composés chimiques, des compositions pharmaceutiques contenant ceux-ci et l'utilisation de ceux-ci dans la fabrication de médicaments utiles pour produire un effet anticancéreux chez un animal à sang chaud et chez 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.