(S)-2-(dimethylamino)-1-phenylethyl 6,6-dimethyl-3-(3,3,3-trifluoro-2,2-dimethylpropanamido)-4,6-dihydropyrrolo[3,4c]pyrazole-5(1H)-carboxylate- | 1375799-69-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-2-(dimethylamino)-1-phenylethyl 6,6-dimethyl-3-(3,3,3-trifluoro-2,2-dimethylpropanamido)-4,6-dihydropyrrolo[3,4c]pyrazole-5(1H)-carboxylate-
• 英文别名: [(1S)-2-(dimethylamino)-1-phenylethyl] 6,6-dimethyl-3-[(3,3,3-trifluoro-2,2-dimethylpropanoyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxylate
• CAS: 1375799-69-1
• 化学式: C₂₃H₃₀F₃N₅O₃
• 分子量: 481.518
• InChiKey: NVGVXGWSXFIODS-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氨基-4,6-二氢-6,6-二甲基-吡咯并[3,4-c]吡唑-1,5-二甲酸 5-叔丁基 1-乙基酯 在 盐酸 、 草酰氯 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 35.33h， 生成 (S)-2-(dimethylamino)-1-phenylethyl 6,6-dimethyl-3-(3,3,3-trifluoro-2,2-dimethylpropanamido)-4,6-dihydropyrrolo[3,4c]pyrazole-5(1H)-carboxylate-
  参考文献：
  名称：

  Discovery of Pyrroloaminopyrazoles as Novel PAK Inhibitors

  摘要：

  The P21-activated kinases (PAK) are emerging antitumor therapeutic targets. In this paper, we describe the discovery of potent PAK inhibitors guided by structure-based drug design. In addition, the efflux of the pyrrolopyrazole series was effectively reduced by applying multiple medicinal chemistry strategies, leading to a series of PAK inhibitors that are orally active in inhibiting tumor growth in vivo.

  DOI：

  10.1021/jm300204j

文献信息

• Discovery of Pyrroloaminopyrazoles as Novel PAK Inhibitors
  作者：Chuangxing Guo、Indrawan McAlpine、Junhu Zhang、Daniel D. Knighton、Susan Kephart、M. Catherine Johnson、Haitao Li、Djamal Bouzida、Anle Yang、Liming Dong、Joseph Marakovits、Jayashree Tikhe、Paul Richardson、Lisa C. Guo、Robert Kania、Martin P. Edwards、Eugenia Kraynov、James Christensen、Joseph Piraino、Joseph Lee、Eleanor Dagostino、Christine Del-Carmen、Ya-Li Deng、Tod Smeal、Brion W. Murray

  DOI：10.1021/jm300204j

  日期：2012.5.24

  The P21-activated kinases (PAK) are emerging antitumor therapeutic targets. In this paper, we describe the discovery of potent PAK inhibitors guided by structure-based drug design. In addition, the efflux of the pyrrolopyrazole series was effectively reduced by applying multiple medicinal chemistry strategies, leading to a series of PAK inhibitors that are orally active in inhibiting tumor growth in vivo.