3-tert-butyl-1-benzyl-N-[4-(hydroxymethyl)thiazol-2-yl]-1H-pyrazole-5-carboxamide | 1341129-00-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-tert-butyl-1-benzyl-N-[4-(hydroxymethyl)thiazol-2-yl]-1H-pyrazole-5-carboxamide
• 英文别名: 2-benzyl-5-tert-butyl-N-[4-(hydroxymethyl)-1,3-thiazol-2-yl]pyrazole-3-carboxamide
• CAS: 1341129-00-7
• 化学式: C₁₉H₂₂N₄O₂S
• 分子量: 370.475
• InChiKey: BKLWXCRJUPADLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-benzyl-3-tert-butyl-N-(4-chloromethylthiazol-2-yl)-1H-pyrazole-5-carboxamide 在 sodium nitrate 作用下， 以 三氟乙酸 为溶剂， 以72%的产率得到3-tert-butyl-1-benzyl-N-[4-(hydroxymethyl)thiazol-2-yl]-1H-pyrazole-5-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