N-(4-(6-bromoquinazolin-2-ylamino)phenyl)-3-methoxypropanamide | 1008506-13-5

• 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: N-(4-(6-bromoquinazolin-2-ylamino)phenyl)-3-methoxypropanamide
• 英文别名: N-[4-[(6-bromoquinazolin-2-yl)amino]phenyl]-3-methoxypropanamide
• CAS: 1008506-13-5
• 化学式: C₁₈H₁₇BrN₄O₂
• 分子量: 401.263
• InChiKey: IAKTYIAZQRUZQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  76.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(4-(6-bromoquinazolin-2-ylamino)phenyl)-3-methoxypropanamide 、 吡啶-4-硼酸 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 12.0h， 生成 3-methoxy-N-(4-(6-(pyridin-4-yl)quinazolin-2-ylamino)phenyl)propanamide
  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：

  tert-butyl {4-[3-methoxypropanoylamino]phenyl}carbamate 在 盐酸 作用下， 以 四氢呋喃 、 水 、 异丙醇 为溶剂， 反应 2.0h， 生成 N-(4-(6-bromoquinazolin-2-ylamino)phenyl)-3-methoxypropanamide
  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：——
• WO2008/68507
  申请人：——

  公开号：——

  公开（公告）日：——