(3-bromo-5-(1H-indol-4-yl)phenyl)(2-chloro-6-methylpyridin-4-yl)methanone | 1260030-04-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3-bromo-5-(1H-indol-4-yl)phenyl)(2-chloro-6-methylpyridin-4-yl)methanone
• 英文别名: [3-bromo-5-(1H-indol-4-yl)phenyl]-(2-chloro-6-methylpyridin-4-yl)methanone
• CAS: 1260030-04-3
• 化学式: C₂₁H₁₄BrClN₂O
• 分子量: 425.712
• InChiKey: BJPQZRDCZFZJJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3-bromo-5-(1H-indol-4-yl)phenyl)(2-chloro-6-methylpyridin-4-yl)methanone 在 copper(l) iodide 、 caesium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 19.0h， 生成 N-(3-(1H-indol-4-yl)-5-(2-methyl-6-morpholinoisonicotinoyl)-phenyl)acetamide
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of N-(3-(1H-Indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a Potent Antimitotic Agent

  摘要：

  The synthesis and optimization of a series of orally bioavailable 1-(1H-indol-4-yl)-3,5-disubstituted benzene analogues as antimitotic agents are described A functionalized dibromobenzene intermediate was used as a key scaffold, which when modified by sequential Suzuki coupling and Buchwald-Hartwig amination provided a flexible entry to 1,3,5-trisubstituted phenyl compounds A 1H-indol-4-yl moiety at the 1-position was determined to be a critical feature for optimal potency The compounds have been shown to induce cell cycle arrest at the G2/M phase and demonstrate efficacy in both cell viability and cell proliferation assays The primary site of action for these agents is revealed by their colchicine competitive inhibition of tubulin polymerization, and a computational model has been developed for the association of these compounds to tubulin An optimized lead LP-261 significantly inhibits growth of a human non-small-cell lung tumor (NCI-H522) in a mouse xenograft model

  DOI：

  10.1021/jm100659v
• 作为产物：
  描述：

  2-氯-6-甲基吡啶-4-羧酸 在 四(三苯基膦)钯 、 正丁基锂 、 sodium carbonate 、 1-羟基苯并三唑 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 34.08h， 生成 (3-bromo-5-(1H-indol-4-yl)phenyl)(2-chloro-6-methylpyridin-4-yl)methanone
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of N-(3-(1H-Indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a Potent Antimitotic Agent

  摘要：

  The synthesis and optimization of a series of orally bioavailable 1-(1H-indol-4-yl)-3,5-disubstituted benzene analogues as antimitotic agents are described A functionalized dibromobenzene intermediate was used as a key scaffold, which when modified by sequential Suzuki coupling and Buchwald-Hartwig amination provided a flexible entry to 1,3,5-trisubstituted phenyl compounds A 1H-indol-4-yl moiety at the 1-position was determined to be a critical feature for optimal potency The compounds have been shown to induce cell cycle arrest at the G2/M phase and demonstrate efficacy in both cell viability and cell proliferation assays The primary site of action for these agents is revealed by their colchicine competitive inhibition of tubulin polymerization, and a computational model has been developed for the association of these compounds to tubulin An optimized lead LP-261 significantly inhibits growth of a human non-small-cell lung tumor (NCI-H522) in a mouse xenograft model

  DOI：

  10.1021/jm100659v

文献信息

• Synthesis and Pharmacological Evaluation of <i>N</i>-(3-(1<i>H</i>-Indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a Potent Antimitotic Agent
  作者：Rupa S. Shetty、Younghee Lee、Bin Liu、Arifa Husain、Rhoda W. Joseph、Yixin Lu、David Nelson、John Mihelcic、Wenchun Chao、Kristofer K. Moffett、Andreas Schumacher、Dietmar Flubacher、Aleksandar Stojanovic、Marina Bukhtiyarova、Ken Williams、Kyoung-Jin Lee、Alexander R. Ochman、Michael S. Saporito、William R. Moore、Gary A. Flynn、Bruce D. Dorsey、Eric B. Springman、Ted Fujimoto、Martha J. Kelly

  DOI：10.1021/jm100659v

  日期：2011.1.13

  The synthesis and optimization of a series of orally bioavailable 1-(1H-indol-4-yl)-3,5-disubstituted benzene analogues as antimitotic agents are described A functionalized dibromobenzene intermediate was used as a key scaffold, which when modified by sequential Suzuki coupling and Buchwald-Hartwig amination provided a flexible entry to 1,3,5-trisubstituted phenyl compounds A 1H-indol-4-yl moiety at the 1-position was determined to be a critical feature for optimal potency The compounds have been shown to induce cell cycle arrest at the G2/M phase and demonstrate efficacy in both cell viability and cell proliferation assays The primary site of action for these agents is revealed by their colchicine competitive inhibition of tubulin polymerization, and a computational model has been developed for the association of these compounds to tubulin An optimized lead LP-261 significantly inhibits growth of a human non-small-cell lung tumor (NCI-H522) in a mouse xenograft model