2-(3,5-dimethyl-pyrazol-1-yl)-6-(4-morpholin-4-yl-pyridin-2-yl)-pyrimidin-4-ylamine | 1061748-43-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-(3,5-dimethyl-pyrazol-1-yl)-6-(4-morpholin-4-yl-pyridin-2-yl)-pyrimidin-4-ylamine
• 英文别名: 2-(3,5-Dimethylpyrazol-1-yl)-6-(4-morpholin-4-ylpyridin-2-yl)pyrimidin-4-amine
• CAS: 1061748-43-3
• 化学式: C₁₈H₂₁N₇O
• 分子量: 351.411
• InChiKey: IBCPSKNBZUSILB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  95
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(3,5-dimethyl-pyrazol-1-yl)-6-(4-morpholin-4-yl-pyridin-2-yl)-pyrimidin-4-ylamine 、 乙酰氯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以12%的产率得到N-[2-(3,5-dimethyl-pyrazol-1-yl)-6-(4-morpholin-4-yl-pyridin-2-yl)-pyrimidin-4-yl]-acetamide
  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
• 作为产物：
  描述：

  2-Hydrazinyl-6-(4-morpholin-4-ylpyridin-2-yl)pyrimidin-4-amine 、 乙酰丙酮 以 乙醇 为溶剂， 反应 1.5h， 以110 mg的产率得到2-(3,5-dimethyl-pyrazol-1-yl)-6-(4-morpholin-4-yl-pyridin-2-yl)-pyrimidin-4-ylamine
  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

文献信息

• SUBSTITUTED PYRIMIDINES AS ADENOSINE RECEPTOR ANTAGONISTS
  申请人：Chen Youngsheng

  公开号：US20100249084A1

  公开（公告）日：2010-09-30

  Compounds of formula (I): wherein R 1 , R 2 and R 3 are as defined herein, including pharmaceutically acceptable salt, ester, solvate or stereoisomer thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof.

  公式(I)的化合物：其中R1，R2和R3的定义如本文所述，包括其药学上可接受的盐，酯，溶剂合物或立体异构体。本发明还揭示了含有该化合物的组合物与药学上可接受的载体的组合物，以及与其有关的使用方法。
• [EN] SUBSTITUTED PYRIMIDINES AS ADENOSINE RECEPTOR ANTAGONISTS<br/>[FR] PYRIMIDINES SUBSTITUÉES UTILISÉES COMME ANTAGONISTES DES RÉCEPTEURS DE L'ADÉNOSINE
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2008116185A2

  公开（公告）日：2008-09-25

  [EN] Compounds of formula(I): wherein R₁, R₂ and R₃ are as defined herein, including pharmaceutically acceptable salt, ester, solvate or stereoisomer thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof.
  [FR] Cette invention se rapporte à des composés de formule (I) dans laquelle R₁, R₂ et R₃ sont tels que définis dans la description, y compris un sel pharmaceutiquement acceptable, un ester, un solvate ou un stéréo-isomère dérivé. L'invention concerne également des compositions contenant un composé de l'invention associé avec un porteur pharmaceutiquement acceptable, ainsi que des procédés associés à leur utilisation.