(R)-tert-butyl 4-(5-(2-aminopyridin-4-yl)-6-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate | 1639881-34-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (R)-tert-butyl 4-(5-(2-aminopyridin-4-yl)-6-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate
• 英文别名: 1,1-Dimethylethyl 4-[(6R)-5-(2-amino-4-pyridinyl)-4,5,6,7-tetrahydro-6-methylpyrazolo[1,5-a]pyrazin-3-yl]-1-piperidinecarboxylate；tert-butyl 4-[(6R)-5-(2-aminopyridin-4-yl)-6-methyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-3-yl]piperidine-1-carboxylate
• CAS: 1639881-34-7
• 化学式: C₂₂H₃₂N₆O₂
• 分子量: 412.535
• InChiKey: CZOKLUNOXMRBSK-OAHLLOKOSA-N

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl 4-(5-(2-aminopyridin-4-yl)-6-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Structure-Based Drug Design of Novel Potent and Selective Tetrahydropyrazolo[1,5-a]pyrazines as ATR Inhibitors

  摘要：

  A saturation strategy focused on improving the selectivity and physicochemical properties of ATR inhibitor HTS hit 1 led to a novel series of highly potent and selective tetrahydropyrazolo[1,5-a]pyrazines. Use of PI3K alpha mutants as ATR crystal structure surrogates was instrumental in providing cocrystal structures to guide the medicinal chemistry designs. Detailed DMPK studies involving cyanide and GSH as trapping agents during microsomal incubations, in addition to deuterium-labeled compounds as mechanistic probes uncovered the molecular basis for the observed CYP3A4 TDI in the series.

  DOI：

  10.1021/ml500353p
• 作为产物：
  描述：

  在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 palladium 10% on activated carbon 、 甲酸铵 、 sodium hydride 、 sodium carbonate 、 lithium hexamethyldisilazane 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 7.5h， 生成 (R)-tert-butyl 4-(5-(2-aminopyridin-4-yl)-6-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Structure-Based Drug Design of Novel Potent and Selective Tetrahydropyrazolo[1,5-a]pyrazines as ATR Inhibitors

  摘要：

  A saturation strategy focused on improving the selectivity and physicochemical properties of ATR inhibitor HTS hit 1 led to a novel series of highly potent and selective tetrahydropyrazolo[1,5-a]pyrazines. Use of PI3K alpha mutants as ATR crystal structure surrogates was instrumental in providing cocrystal structures to guide the medicinal chemistry designs. Detailed DMPK studies involving cyanide and GSH as trapping agents during microsomal incubations, in addition to deuterium-labeled compounds as mechanistic probes uncovered the molecular basis for the observed CYP3A4 TDI in the series.

  DOI：

  10.1021/ml500353p