4-cyano-1-cyclohexyl-8-methoxy-3-methyl-imidazo[1,5-a]pyrido[3,2-e]pyrazine | 1156500-43-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并[1,5-a]吡嗪
• 英文名称: 4-cyano-1-cyclohexyl-8-methoxy-3-methyl-imidazo[1,5-a]pyrido[3,2-e]pyrazine
• 英文别名: 9-cyclohexyl-2-methoxy-7-methylimidazo[1,5-a]pyrido[3,2-e]pyrazine-6-carbonitrile；4-Cyano-1-cyclohexyl-8-methoxy-3-methyl-imidazo[1,5-a]pyrido-[3,2-e]pyrazine；3-cyclohexyl-12-methoxy-5-methyl-2,4,8,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-7-carbonitrile
• CAS: 1156500-43-4
• 化学式: C₁₈H₁₉N₅O
• 分子量: 321.382
• InChiKey: IDBPPELBLKXMMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  76.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  potassium cyanide 、 7-Chloro-3-cyclohexyl-12-methoxy-5-methyl-2,4,8,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene 在 ethoxycarbonyldifluoromethyl magnesia chloride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以74%的产率得到4-cyano-1-cyclohexyl-8-methoxy-3-methyl-imidazo[1,5-a]pyrido[3,2-e]pyrazine
  参考文献：
  名称：

  Discovery of Imidazo[1,5-a]pyrido[3,2-e]pyrazines as a New Class of Phosphodiesterase 10A Inhibitiors

  摘要：

  Novel imidazo[1,5-a]pyrido[3,2-e]pyrazines have been synthesized and characterized as both potent and selective phosphodiesterase 10A (PDE10A) inhibitors. For in vitro characterization, inhibition of PDE10A mediated cAMP hydrolysis was used and a QSAR model was established to analyze substitution effects. The outcome of this analysis was complemented by the crystal structure of PDE10A in complex with compound 49. Qualitatively new interactions between inhibitor and binding site were found, contrasting with previously published crystal structures of papaverine-like inhibitors. In accordance with the known antipsychotic potential of PDE10A inhibitors, MK-801 induced stereotypy and hyperactivity in rats were reversed by selected compounds. Thus, a promising compound class has been identified for the treatment of schizophrenia that could circumvent side effects connected with current therapies.

  DOI：

  10.1021/jm1002793

文献信息

• Pyrido[3,2-E]Pyrazines, Process For Preparing The Same, And Their Use As Inhibitors Of Phosphodiesterase 10
  申请人：Malamas Michael S.

  公开号：US20090143361A1

  公开（公告）日：2009-06-04

  The invention relates to pyrido[3,2-e]pyrazines, to processes for preparing them, to pharmaceutical compositions which comprise these compounds and to the pharmaceutical use of these compounds, which are inhibitors of phosphodiesterase 10, as active compounds for treating central nervous system disorders, obesity, and metabolic disorders.

  这项发明涉及吡啶并[3,2-e]吡嗪化合物，涉及其制备方法，包括这些化合物的药物组成物以及这些化合物的药用，这些化合物是磷酸二酯酶10的抑制剂，作为治疗中枢神经系统疾病、肥胖和代谢紊乱的活性化合物。
• [EN] PYRIDO[3,2-E]PYRAZINES, PROCESS FOR PREPARING THE SAME, AND THEIR USE AS INHIBITORS OF PHOSPHODIESTERASE 10<br/>[FR] PYRIDO[3,2-E]PYRAZINES, LEUR PROCÉDÉ DE PRÉPARATION, ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PHOSPHODIESTÉRASE 10
  申请人：WYETH CORP

  公开号：WO2009070583A1

  公开（公告）日：2009-06-04

  The invention relates to pyrido[3,2-e]pyrazines, to processes for preparing them, to pharmaceutical compositions which comprise these compounds and to the pharmaceutical use of these compounds, which are inhibitors of phosphodiesterase 10, as active compounds for treating central nervous system disorders, obesity, and metabolic disorders.