N-[2-(3,5-dimethyl-pyrazol-1-yl)-6-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-6'-yl)-pyrimidin-4-yl]-acetamide trifluoroacetate | 1061748-02-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-[2-(3,5-dimethyl-pyrazol-1-yl)-6-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-6'-yl)-pyrimidin-4-yl]-acetamide trifluoroacetate
• 英文别名: N-(2-(3,5-dimethyl-pyrazol-1-yl)-6-{6-(piperidin-1-yl)-pyridin-2-yl}-pyrimidin-4-yl)-acetamide trifluoroacetate；N-[2-(3,5-dimethylpyrazol-1-yl)-6-(6-piperidin-1-ylpyridin-2-yl)pyrimidin-4-yl]acetamide;2,2,2-trifluoroacetic acid
• CAS: 1061748-02-4
• 化学式: C₂HF₃O₂*C₂₁H₂₅N₇O
• 分子量: 505.5
• InChiKey: LREANJYWRXRADE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.92
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  哌啶 、 N-[6-(6-chloropyridin-2-yl)-2-(3,5-dimethyl-pyrazol-1-yl)-pyrimidin-4-yl]-acetamide 、 三氟乙酸 以 N,N-二甲基乙酰胺 、 水 、 乙腈 为溶剂， 反应 0.33h， 以5%的产率得到N-[2-(3,5-dimethyl-pyrazol-1-yl)-6-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-6'-yl)-pyrimidin-4-yl]-acetamide trifluoroacetate
  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