1-methyl-4-[(3E)-4-(tri-n-butylstannyl)but-3-enyl]piperazine | 946490-41-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-methyl-4-[(3E)-4-(tri-n-butylstannyl)but-3-enyl]piperazine
• 英文别名: 1-methyl-4-[(3E)-4-(tributylstannyl)but-3-enyl]piperazine；SKI-606；1-methyl-4-(4-tributylstannanyl-but-3-enyl)-piperazine
• CAS: 946490-41-1
• 化学式: C₂₁H₄₄N₂Sn
• 分子量: 443.304
• InChiKey: HJHXBGTZMKWNHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.57
• 重原子数：
  24
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-({3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}amino)-3-cyano-6-methoxyquinolin-7-yl trifluoromethanesulfonate 、 1-methyl-4-[(3E)-4-(tri-n-butylstannyl)but-3-enyl]piperazine 生成 4-({3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}-amino)-6-methoxy-7-[(1E)-4-(4-methylpiperazin-1-yl)but-1-enyl]quinoline-3-carbonitrile
  参考文献：
  名称：

  PREPARATION OF 7-ALKENYL-3 QUINOLINECARBONITRILES VIA A PALLADIUM MEDIATED COUPLING REACTION

  摘要：

  本发明涉及一种制备式（I）化合物的过程：其中A、R1-R3、X、s、t、u、m和Z在此定义，包括在Pd（O）金属存在下将式（II）试剂与式（III）化合物或其盐反应的步骤。本发明的另一个方面是一种制备式（VI）化合物的方法。

  公开号：

  US20090099356A1
• 作为产物：
  描述：

  三正丁基氢锡 、 1-(3-丁炔-1-基)-4-甲基哌嗪 在 偶氮二异丁腈 作用下， 反应 2.0h， 生成 1-methyl-4-[(3E)-4-(tri-n-butylstannyl)but-3-enyl]piperazine
  参考文献：
  名称：

  Quinazoline derivatives

  摘要：

  式（I）的化合物或其药学上可接受的盐、水合物、溶剂合物、光学活性化合物、消旋体或其二对映异构体混合物具有优越的酪氨酸特异性蛋白激酶抑制活性，并且可用作药物剂，特别是作为各种癌症、银屑病或由动脉硬化引起的疾病的预防或治疗剂。

  公开号：

  US20040116422A1

文献信息

• Optimization of 7-alkene-3-quinolinecarbonitriles as Src kinase inhibitors
  作者：Diane H. Boschelli、Daniel Wang、Yan Wang、Biqi Wu、Erick E. Honores、Ana Carolina Barrios Sosa、Inder Chaudhary、Jennifer Golas、Judy Lucas、Frank Boschelli

  DOI：10.1016/j.bmcl.2010.03.025

  日期：2010.5

  The 7-alkene-3-quinolinecarbonitrile 20, a potent inhibitor of Src enzymatic and cellular activity with IC50 values of 2.1 and 58 nM, respectively, had comparable efficacy to bosutinib in a colon tumor xenograft study. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis of 7-(E)-alkenyl-4-amino-3-quinolinecarbonitriles via Pd-mediated Heck, Stille, and Suzuki reactions
  作者：Yanong D. Wang、Minu Dutia、M. Brawner Floyd、Amar S. Prashad、Dan Berger、Melissa Lin

  DOI：10.1016/j.tet.2008.10.063

  日期：2009.1

  A regio- and stereoselective synthesis of 7-(E)-alkenyl-4-amino-3-quinolinecarbonitriles via Pd-mediated coupling reactions was developed. The comparison and optimization of stereoselectivity of the Heck, Stille, and Suzuki reactions of 7-bromo or 7-triflate-3-quinolinecarbonitrile are described. Compound 7 and 10 were potent inhibitors of Src kinase and Raf/Mek activity, respectively. (C) 2008 Elsevier Ltd. All rights reserved.
• 4-Anilino-7-alkenylquinoline-3-carbonitriles as potent MEK1 kinase inhibitors
  作者：Dan M. Berger、Minu Dutia、Dennis Powell、Middleton B. Floyd、Nancy Torres、Robert Mallon、Donald Wojciechowicz、Steven Kim、Larry Feldberg、Karen Collins、Inder Chaudhary

  DOI：10.1016/j.bmc.2008.09.009

  日期：2008.10

  A series of substituted 7-alkenyl 4[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)]anilino-3-quinolinecarbonitrile analogs were synthesized and evaluated as MEK1 kinase inhibitors. The synthetic details, structure-activity relationships, biological activity, and selected oral exposure studies of these analogs are described. From these studies, compound 5m was chosen as a strong candidate for further evaluation. The selectivity of 5m was ascertained against a panel of 17 kinases, where activity was observed against EGFR, Src, Lyn, and IR kinases. Western blot studies in WM-266 cells demonstrated that 5m inhibited phosphorylation of ERK, while additional kinase pathways tested showed no inhibition at up to 10 mu M of 5m. PK studies, as well as a xenograft and in vivo biomarker studies are described for 5m. (C) 2008 Elsevier Ltd. All rights reserved.