2-methyl-6-(methylthio)-3-nitropyridine | 66665-87-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-methyl-6-(methylthio)-3-nitropyridine
• 英文别名: 2-Methylthio-5-nitro-6-methylpyridin；2-methyl-6-methylsulfanyl-3-nitro-pyridine；2-Methyl-6-methylsulfanyl-3-nitropyridine
• CAS: 66665-87-0
• 化学式: C₇H₈N₂O₂S
• 分子量: 184.219
• InChiKey: XVKVRSNYNYFKJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  84
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-methyl-6-(methylthio)-3-nitropyridine 在 盐酸 、 溶剂黄146 、 锌 作用下， 以 水 为溶剂， 反应 2.0h， 以80%的产率得到2-methyl-6-(methylthio)pyridin-3-amine
  参考文献：
  名称：

  Syntheses and pharmacokinetic evaluations of four metabolites of 2-(4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazin-1-yl)-N-(6-methyl-2,4-bis-(methylthio)pyridin-3-yl)acetamide hydrochloride [K-604], an acyl-CoA:cholesterol O-acyltransferase-1 inhibitor

  摘要：

  We synthesized and identified four metabolites of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT)-1 inhibitor, K-604 (1). Two of the metabolites M1 and M2, were prepared from 1 using a combination reagent of hydrogen peroxide and sodium tungstate with either phosphoric acid or trifluoroethanol as the solvent to control the regioselectivity. Upon exposure of 4b to tert-butyl hypochlorite at -78 degrees C, the monosulfoxidation afforded synthetic intermediate of M3 in excellent yield. The efficient synthesis of M4 was established. The in vitro metabolic study exhibited a high clearance value (720 mu L/min/mg protein) of 1 using human liver microsomes. We orally administered a single dose of 10 mg/kg of 1 to monkeys because the in vitro metabolic patterns are quite similar. Fortunately, the drug concentration of 1 was much higher than those of M1, M2, M3 and M4.

  DOI：

  10.1016/j.bmc.2020.115457
• 作为产物：
  描述：

  2-氨基-5-硝基-6-甲基吡啶 在 硫酸 、 水 、 二乙胺 、 sodium nitrite 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 13.5h， 生成 2-methyl-6-(methylthio)-3-nitropyridine
  参考文献：
  名称：

  Syntheses and pharmacokinetic evaluations of four metabolites of 2-(4-(2-((1H-benzo[d]imidazol-2-yl)thio)ethyl)piperazin-1-yl)-N-(6-methyl-2,4-bis-(methylthio)pyridin-3-yl)acetamide hydrochloride [K-604], an acyl-CoA:cholesterol O-acyltransferase-1 inhibitor

  摘要：

  We synthesized and identified four metabolites of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT)-1 inhibitor, K-604 (1). Two of the metabolites M1 and M2, were prepared from 1 using a combination reagent of hydrogen peroxide and sodium tungstate with either phosphoric acid or trifluoroethanol as the solvent to control the regioselectivity. Upon exposure of 4b to tert-butyl hypochlorite at -78 degrees C, the monosulfoxidation afforded synthetic intermediate of M3 in excellent yield. The efficient synthesis of M4 was established. The in vitro metabolic study exhibited a high clearance value (720 mu L/min/mg protein) of 1 using human liver microsomes. We orally administered a single dose of 10 mg/kg of 1 to monkeys because the in vitro metabolic patterns are quite similar. Fortunately, the drug concentration of 1 was much higher than those of M1, M2, M3 and M4.

  DOI：

  10.1016/j.bmc.2020.115457

文献信息

• TALIK T.; TALIK Z., POL. J. CHEM., 1978, 52, NO 1, 163-170
  作者：TALIK T.、 TALIK Z.

  DOI：——

  日期：——