[2-(3,5-dimethyl-pyrazol-1-yl)-6-(5-methoxy-pyridin-3-yl)-pyrimidin-4-yl]-carbamic acid methyl ester | 1082056-63-0

• 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: [2-(3,5-dimethyl-pyrazol-1-yl)-6-(5-methoxy-pyridin-3-yl)-pyrimidin-4-yl]-carbamic acid methyl ester
• 英文别名: methyl N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(5-methoxypyridin-3-yl)pyrimidin-4-yl]carbamate；methyl N-[2-(3,5-dimethylpyrazol-1-yl)-6-(5-methoxypyridin-3-yl)pyrimidin-4-yl]carbamate
• CAS: 1082056-63-0
• 化学式: C₁₇H₁₈N₆O₃
• 分子量: 354.368
• InChiKey: OIGKTTFTKCPYQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  甲醇 、 以 二氯甲烷 为溶剂， 反应 68.0h， 以52 mg的产率得到[2-(3,5-dimethyl-pyrazol-1-yl)-6-(5-methoxy-pyridin-3-yl)-pyrimidin-4-yl]-carbamic acid methyl ester
  参考文献：
  名称：

  Lead Optimization of 4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A_2A Adenosine Receptor Antagonists for the Treatment of Parkinson’s Disease

  摘要：

  4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-pyrimidines bearing substituted pyridyl groups as C-6 substituents were prepared as selective adenosine hA(2A) receptor antagonists for the treatment of Parkinson's disease. The 5-methoxy-3-pyridyl derivative 6g (hA(2A) K-i 2.3 nM, hA(1) K-i 190 nM) was orally active at 3 mg/kg in a rat HIC model but exposure was poor in nonrodent species, presumably due to poor aqueous solubility. Follow-on compound 16a (hA(2A) K-i 0.83 nM, hA(1) K-i 130 nM), bearing a 6-(morpholin-4-yl)-2-pyridyl substituent at C-6, had improved solubility and was orally efficacious (3 mg/kg, HIC) but showed time-dependent cytochrome P450 3A4 inhibition, possibly related to morpholine ring metabolism. Compound 16j (hA(2A) K-i 0.44 nM, hA(1) K-i 80 nM), bearing a 6-(4-methoxypiperidin-1-yl)-2-pyridyl substituent at C-6, was sparingly soluble but had good oral exposure in rodent and nonrodent species, had no cytochrome P450 or human ether-a-go-go related gene channel issues, and was orally efficacious at 1 mg/kg in HIC and at 3 mg/kg for potentiation Of L-dopa-induced contralateral rotations in 6-hydroxydopamine-lesioned rats.

  DOI：

  10.1021/jm800851u