乙酰胺,N-[3-(3-氰基-4,5-二氢-5-羰基吡唑并[1,5-a]嘧啶-7-基)苯基]- | 159225-98-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 乙酰胺,N-[3-(3-氰基-4,5-二氢-5-羰基吡唑并[1,5-a]嘧啶-7-基)苯基]-
• 英文名称: CL 345644
• 英文别名: N-[3-(3-cyano-4,5-dihydro-5-oxopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-acetamide；desethyl-5-oxo-zaleplon；N-desethyl-5-oxo-zaleplon；desethyl-5-oxo-ZAL；5-Oxo-N-deethylzaleplon；N-[3-(3-cyano-5-oxo-4H-pyrazolo[1,5-a]pyrimidin-7-yl)phenyl]acetamide
• CAS: 159225-98-6
• 化学式: C₁₅H₁₁N₅O₂
• 分子量: 293.285
• InChiKey: JUIDXHFSZAVPIJ-UHFFFAOYSA-N

物化性质

• 沸点：
  571.8±50.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  99.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  乙酰胺,N-[3-(3-氰基-4,5-二氢-5-羰基吡唑并[1,5-a]嘧啶-7-基)苯基]-N-乙基- 在 cytochrome P₄₅₀ human liver microsomes 作用下， 以 phosphate buffer 为溶剂， 反应 0.5h， 生成 乙酰胺,N-[3-(3-氰基-4,5-二氢-5-羰基吡唑并[1,5-a]嘧啶-7-基)苯基]-
  参考文献：
  名称：

  Metabolism of Zaleplon by human hepatic microsomal cytochrome P450 isoforms

  摘要：

  1. The metabolism of Zaleplon (CL-284,846; ZAL) has been studied in human liver microsomal preparations and in cDNA-expressed human cytochrome P450 (CYP) isoforms.2. Human liver microsomes catalysed the NADPH-dependent N-deethylation of ZAL to DZAL (CL-284,859), but not to two other known in vivo metabolites, namely M1 (CL-345,644) and M2 (CL-345,905). Sigmoidal kinetic plots were observed for ZAL deethylation indicating positive cooperativity.3. The metabolism of ZAL to DZAL was determined in a characterized bank of 24 human liver microsomal preparations. Good correlations (r(2) = 0.734-0.937) were observed with caffeine 8-hydroxylase, diazepam 3-hydroxylase, dextromethorphan N-demethylase and testosterone 2 beta-, 6 beta- and 15 beta-hydroxylase activities, which are all catalysed by CYP3A isoforms. In contrast, poor correlations (r(2) = 0.152-0.428) were observed for enzymatic markers for CYP1A2, CYP2A6, CYP2C9/10, CYP2D6, CYP2E1 and CYP4A9/11.4. The metabolism of ZAL to DZAL in human liver microsomes was inhibited to 6-15 % of control by 5-50 mu M of the mechanism-based CYP3A inhibitor troleandomycin. Whereas some inhibition of DZAL formation was observed in the presence of 200 mu M diethyldithiocarbamate, 5-50 mu M furafylline, 2-20 mu M sulphaphenazole, 50-500 mu M S-mephenytoin and 1-10 mu M quinidine had little effect.5. Using human B-lymphoblastoid cell microsomes containing cDNA-expressed CYP isoforms, ZAL was metabolized to DZAL by CYP3A4, but not to any great extent by CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1.6. In contrast with ZAL, the NADPH-dependent N-deethylation of M2 to M1 proceeded at only a very low rate with both human liver microsomes and cDNA-expressed CYP3A4.7. In summary, by correlation analysis, chemical inhibition studies and the use of cDNA-expressed CYPs, ZAL N-deethylation to DZAL in human liver appears to be catalysed by CYP3A isoforms.

  DOI：

  10.1080/004982598239452