di-tert-butyl [(Z)-({5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl}amino)methylylidene]biscarbamate | 1351438-89-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: di-tert-butyl [(Z)-({5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl}amino)methylylidene]biscarbamate
• 英文别名: Carbamic acid, N-[[[5-[3-(dimethylamino)propyl]-2-methyl-3-pyridinyl]amino][[(1,1-dimethylethoxy)carbonyl]amino]methylene]-, 1,1-dimethylethyl ester, [N(Z)]-；tert-butyl N-[N'-[5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
• CAS: 1351438-89-5
• 化学式: C₂₂H₃₇N₅O₄
• 分子量: 435.567
• InChiKey: ZFBCKOWJEKFUQC-UHFFFAOYSA-N

物化性质

• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.11
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  105.15
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  di-tert-butyl [(Z)-({5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl}amino)methylylidene]biscarbamate 在 吡啶 、 盐酸 、 tetraphosphorus decasulfide 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 生成 MLN0905; 2-[[5-[3-(二甲基氨基)丙基]-2-甲基-3-吡啶基]氨基]-5,7-二氢-9-(三氟甲基)- 6H-嘧啶并[5,4-d][1]苯并氮杂卓-6-硫酮
  参考文献：
  名称：

  Discovery of a Potent and Orally Bioavailable Benzolactam-Derived Inhibitor of Polo-Like Kinase 1 (MLN0905)

  摘要：

  This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.

  DOI：

  10.1021/jm2011172
• 作为产物：
  描述：

  N-{5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl}guanidine 、 N,N'-bis-Boc-S-methyl-isothiourea 在 mercury (II) chloride 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以67%的产率得到di-tert-butyl [(Z)-({5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl}amino)methylylidene]biscarbamate
  参考文献：
  名称：

  Discovery of a Potent and Orally Bioavailable Benzolactam-Derived Inhibitor of Polo-Like Kinase 1 (MLN0905)

  摘要：

  This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.

  DOI：

  10.1021/jm2011172