2-(3-furylmethylamino)-6-chloropyrazine

• 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: 2-(3-furylmethylamino)-6-chloropyrazine
• 英文别名: 6-chloro-N-(furan-3-ylmethyl)pyrazin-2-amine
• 化学式: C₉H₈ClN₃O
• 分子量: 209.635
• InChiKey: PMPKFKKHZULNEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  51
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-furylmethylamino)-6-chloropyrazine 、 3-乙酰胺基苯硼酸 在 PdCl₂[1,3-bis(diphenylphosphino)propane]*CH₂Cl₂ 、 sodium carbonate 作用下， 以 乙二醇二甲醚 为溶剂， 反应 18.0h， 以48.7%的产率得到2-(3-Furylmethylamino)-6-(3-acetamidophenyl)pyrazine
  参考文献：
  名称：

  Novel Inhibitors of B-RAF Based on a Disubstituted Pyrazine Scaffold. Generation of a Nanomolar Lead

  摘要：

  B-RAF, a serine/threonine kinase, plays an important role in the development of certain classes of cancer, especially melanoma. As a result of high-throughput screening of a 23,000 compound library, 2-(3,4,5-trimethoxyphenylamino)-6-(3-acetamidophenyl)pyrazine, 1, was identified as a low micromolar (IC50 = 3.5 mu M) B-RAF inhibitor. This compound was chosen as the starting point of a program aimed at producing potent inhibitors of B-RAF. We have synthesized a series of 40 novel compounds, which involved extensive modifications to the 2-(3,4,5-trimethoxyphenylamino) moiety (ring A) of 1. Their biological profiles against isolated B-RAF and mutated B-RAF in a cellular assay have been determined. These efforts led to the identification of two compounds exhibiting activities lower than 800 nM against B-RAF.

  DOI：

  10.1021/jm050983g
• 作为产物：
  描述：

  2,6-二氯吡嗪 、 3-呋喃基甲胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以50.5%的产率得到2-(3-furylmethylamino)-6-chloropyrazine
  参考文献：
  名称：

  Novel Inhibitors of B-RAF Based on a Disubstituted Pyrazine Scaffold. Generation of a Nanomolar Lead

  摘要：

  B-RAF, a serine/threonine kinase, plays an important role in the development of certain classes of cancer, especially melanoma. As a result of high-throughput screening of a 23,000 compound library, 2-(3,4,5-trimethoxyphenylamino)-6-(3-acetamidophenyl)pyrazine, 1, was identified as a low micromolar (IC50 = 3.5 mu M) B-RAF inhibitor. This compound was chosen as the starting point of a program aimed at producing potent inhibitors of B-RAF. We have synthesized a series of 40 novel compounds, which involved extensive modifications to the 2-(3,4,5-trimethoxyphenylamino) moiety (ring A) of 1. Their biological profiles against isolated B-RAF and mutated B-RAF in a cellular assay have been determined. These efforts led to the identification of two compounds exhibiting activities lower than 800 nM against B-RAF.

  DOI：

  10.1021/jm050983g

文献信息

• Novel Inhibitors of B-RAF Based on a Disubstituted Pyrazine Scaffold. Generation of a Nanomolar Lead
  作者：Ion Niculescu-Duvaz、Esteban Roman、Steven R. Whittaker、Frank Friedlos、Ruth Kirk、Ian J. Scanlon、Lawrence C. Davies、Dan Niculescu-Duvaz、Richard Marais、Caroline J. Springer

  DOI：10.1021/jm050983g

  日期：2006.1.1

  B-RAF, a serine/threonine kinase, plays an important role in the development of certain classes of cancer, especially melanoma. As a result of high-throughput screening of a 23,000 compound library, 2-(3,4,5-trimethoxyphenylamino)-6-(3-acetamidophenyl)pyrazine, 1, was identified as a low micromolar (IC50 = 3.5 mu M) B-RAF inhibitor. This compound was chosen as the starting point of a program aimed at producing potent inhibitors of B-RAF. We have synthesized a series of 40 novel compounds, which involved extensive modifications to the 2-(3,4,5-trimethoxyphenylamino) moiety (ring A) of 1. Their biological profiles against isolated B-RAF and mutated B-RAF in a cellular assay have been determined. These efforts led to the identification of two compounds exhibiting activities lower than 800 nM against B-RAF.