8-acetyl-4-(N-methyl-N-phenylamino)-2-(methylsulfanyl)pyrazolo[1,5-a]-1,3,5-triazine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 8-acetyl-4-(N-methyl-N-phenylamino)-2-(methylsulfanyl)pyrazolo[1,5-a]-1,3,5-triazine
• 英文别名: 8-acetyl-4-(N-methyl-N-phenylamino)-2-methylsulfanylpyrazolo[1,5-a]-1,3,5-triazine；1-[4-(Methyl-phenyl-amino)-2-methylsulfanyl-pyrazolo[1,5-a][1,3,5]triazin-8-yl]-ethanone；1-[4-(N-methylanilino)-2-methylsulfanylpyrazolo[1,5-a][1,3,5]triazin-8-yl]ethanone
• 化学式: C₁₅H₁₅N₅OS
• 分子量: 313.383
• InChiKey: BOSIOOIHFYRLOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  88.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-acetyl-4-(N-methyl-N-phenylamino)-2-(methylsulfanyl)pyrazolo[1,5-a]-1,3,5-triazine 、 甲基溴化镁 在 sodium tetrahydroborate 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 以89%的产率得到4-(N-methyl-N-phenylamino)-8-(1-methylethyl)-2-(methylsulfanyl)pyrazolo[1,5-a]-1,3,5-triazine
  参考文献：
  名称：

  Pyrazolo[1,5-a]-1,3,5-triazine as a Purine Bioisostere: Access to Potent Cyclin-Dependent Kinase Inhibitor (R)-Roscovitine Analogue

  摘要：

  Pharmacological inhibitors of cyclin-dependent kinases (CDKs) have a wide therapeutic potential. Among the CDK inhibitors currently under clinical trials, the 2,6,9-trisubstituted purine (R)-roscovitine displays rather high selectivity, low toxicity, and promising antitumor activity. In an effort to improve this structure, we synthesized several bioisosteres of roscovitine. Surprisingly, one of them, pyrazolo[1,5-a]-1,3,5-triazine 7a (N-&-N1, GP0210), displayed significantly higher potency, compared to (R)-roscovitine and imidazo[2,1-f]-1,2,4-triazine 13 (N-&-N2, GP0212), at inhibiting various CDKs and at inducing cell death in a wide variety of human tumor cell lines. This approach may thus provide second generation analogues with enhanced biomedical potential.

  DOI：

  10.1021/jm801340z
• 作为产物：
  描述：

  2-(甲基硫代)吡唑并[1,5-a][1,3,5]噻嗪-4(3H)-酮 在 四(三苯基膦)钯 4-二甲氨基吡啶 、 N-碘代丁二酰亚胺 、 lithium chloride 、 三氯氧磷 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 8-acetyl-4-(N-methyl-N-phenylamino)-2-(methylsulfanyl)pyrazolo[1,5-a]-1,3,5-triazine
  参考文献：
  名称：

  钯催化交叉偶联反应合成8-取代吡唑并[1,5-a]-1,3,5-三嗪衍生物

  摘要：

  8-取代的吡唑并[1,5-a]-1,3,5-三嗪衍生物6由相应的8-碘吡唑并[1,5-a]-1,3,5-三嗪5通过钯催化交叉制备-偶联反应。然后通过最终的亲核芳香取代制备了几种次黄嘌呤药物 2 的生物等排体。

  DOI：

  10.1055/s-2006-958963

文献信息

• Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives
  作者：Florence Popowycz、Cédric Schneider、Salvatore DeBonis、Dimitrios A. Skoufias、Frank Kozielski、Carlos M. Galmarini、Benoît Joseph

  DOI：10.1016/j.bmc.2009.03.007

  日期：2009.5

  Pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives 1a–c were prepared from 4-(N-methyl-N-phenylamino)-2-methylsulfanylpyrazolo[1,5-a]-1,3,5-triazine 2. Their cytotoxic activity, inhibition of tubulin polymerization, and cell cycle effects were evaluated. Compounds 1a and 1c are potent tubulin inhibitors and displayed specific antiproliferative activity in colorectal cancer cell lines at micromolar

  吡唑并[1,5-一个] -1,3,5-三嗪衍生物myoseverin 1A-1C是从4-（制备Ñ甲基ñ -苯基氨基）-2- methylsulfanylpyrazolo [1,5-一个] -1,3- ，5-三嗪2。他们的细胞毒性活性，微管蛋白聚合的抑制作用和细胞周期的影响进行了评估。化合物1a和1c是有效的微管蛋白抑制剂，在大摩尔浓度下，在大肠癌细胞系中显示出特定的抗增殖活性。
• Pyrazolo[1,5-<i>a</i>]-1,3,5-triazine as a Purine Bioisostere: Access to Potent Cyclin-Dependent Kinase Inhibitor (<i>R</i>)-Roscovitine Analogue
  作者：Florence Popowycz、Guy Fournet、Cédric Schneider、Karima Bettayeb、Yoan Ferandin、Cyrile Lamigeon、Oscar M. Tirado、Silvia Mateo-Lozano、Vicente Notario、Pierre Colas、Philippe Bernard、Laurent Meijer、Benoît Joseph

  DOI：10.1021/jm801340z

  日期：2009.2.12

  Pharmacological inhibitors of cyclin-dependent kinases (CDKs) have a wide therapeutic potential. Among the CDK inhibitors currently under clinical trials, the 2,6,9-trisubstituted purine (R)-roscovitine displays rather high selectivity, low toxicity, and promising antitumor activity. In an effort to improve this structure, we synthesized several bioisosteres of roscovitine. Surprisingly, one of them, pyrazolo[1,5-a]-1,3,5-triazine 7a (N-&-N1, GP0210), displayed significantly higher potency, compared to (R)-roscovitine and imidazo[2,1-f]-1,2,4-triazine 13 (N-&-N2, GP0212), at inhibiting various CDKs and at inducing cell death in a wide variety of human tumor cell lines. This approach may thus provide second generation analogues with enhanced biomedical potential.
• Synthesis of 8-Substituted Pyrazolo[1,5-<i>a</i>]-1,3,5-triazine Derivatives by Palladium-Catalyzed Cross-Coupling Reactions
  作者：Benoît Joseph、Florence Popowycz、Philippe Bernard、Pierre Raboisson

  DOI：10.1055/s-2006-958963

  日期：2007.2

  8-Substituted pyrazolo[1,5-a]-1,3,5-triazine derivatives 6 were prepared from the corresponding 8-iodopyrazolo[1,5-a]-1,3,5-triazines 5 through palladium-catalyzed cross-coupling reactions. Several bioisosteres of hypoxanthine drugs 2 were then prepared by final nucleophilic aromatic substitution.

  8-取代的吡唑并[1,5-a]-1,3,5-三嗪衍生物6由相应的8-碘吡唑并[1,5-a]-1,3,5-三嗪5通过钯催化交叉制备-偶联反应。然后通过最终的亲核芳香取代制备了几种次黄嘌呤药物 2 的生物等排体。