tert-butyl ((2-(pyrimidine-2-carboxamido)thiazol-4-yl)methyl)carbamate | 1341129-86-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: tert-butyl ((2-(pyrimidine-2-carboxamido)thiazol-4-yl)methyl)carbamate
• CAS: 1341129-86-9
• 化学式: C₁₄H₁₇N₅O₃S
• 分子量: 335.387
• InChiKey: JXQNPTQFEDZGDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.21
• 重原子数：
  23.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  106.1
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl ((2-(pyrimidine-2-carboxamido)thiazol-4-yl)methyl)carbamate 在 Amberlyst A-21 resin 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 N-(4-(aminomethyl)thiazol-2-yl)pyrimidine-2-carboxamide
  参考文献：
  名称：

  Novel Orally Active Antimalarial Thiazoles

  摘要：

  An aminomethylthiazole pyrazole carboxamide lead 3 with good in vitro antiplasmodial activity [IC50: 0.08 mu M (K1, chloroquine and multidrug resistant strain) and 0.07 mu M (NF54, chloroquine sensitive strain)] and microsomal metabolic stability was identified from whole cell screening of a SoftFocus kinase library. Compound 3 also exhibited in vivo activity in the P. berghei mouse model at 4 x 50 mg/kg administration via the oral route, showing 99.5% activity and 9 days survival and showed low in vitro cytotoxicity. Pharmacokinetic studies in rats revealed good oral bioavailability (51% at 22 mg/kg) with a moderate rate of absorption, reasonable half-life (t(1/2) 3 h), and high volume of distribution with moderately high plasma and blood clearance after IV administration. Toward toxicity profiling, 3 exhibited moderate potential to inhibit CYP1A2 (IC50 = 1.5 mu M) and 2D6 (IC50 = 0.4 mu M) as well as having a potential hERG liability (IC50 = 3.7 mu M).

  DOI：

  10.1021/jm201108k
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 tert-butyl ((2-(pyrimidine-2-carboxamido)thiazol-4-yl)methyl)carbamate
  参考文献：
  名称：

  Novel Orally Active Antimalarial Thiazoles

  摘要：

  An aminomethylthiazole pyrazole carboxamide lead 3 with good in vitro antiplasmodial activity [IC50: 0.08 mu M (K1, chloroquine and multidrug resistant strain) and 0.07 mu M (NF54, chloroquine sensitive strain)] and microsomal metabolic stability was identified from whole cell screening of a SoftFocus kinase library. Compound 3 also exhibited in vivo activity in the P. berghei mouse model at 4 x 50 mg/kg administration via the oral route, showing 99.5% activity and 9 days survival and showed low in vitro cytotoxicity. Pharmacokinetic studies in rats revealed good oral bioavailability (51% at 22 mg/kg) with a moderate rate of absorption, reasonable half-life (t(1/2) 3 h), and high volume of distribution with moderately high plasma and blood clearance after IV administration. Toward toxicity profiling, 3 exhibited moderate potential to inhibit CYP1A2 (IC50 = 1.5 mu M) and 2D6 (IC50 = 0.4 mu M) as well as having a potential hERG liability (IC50 = 3.7 mu M).

  DOI：

  10.1021/jm201108k