N³-(R)-(-)-α-hydroxy-β-phenethyluridine | 183623-31-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: N³-(R)-(-)-α-hydroxy-β-phenethyluridine
• 英文别名: 3-[(2R)-2-Hydroxy-2-phenylethyl]uridine；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3-[(2R)-2-hydroxy-2-phenylethyl]pyrimidine-2,4-dione
• CAS: 183623-31-6
• 化学式: C₁₇H₂₀N₂O₇
• 分子量: 364.355
• InChiKey: CMHUTFXSVUSLGG-OVJXPFRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  131
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-[(2R,3R,4S,5R)-3,4-二羟基-5-(羟基甲基)四氢呋喃-2-基]-3-(2-氧代-2-苯基乙基)嘧啶-2,4-二酮 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 N³-(R)-(-)-α-hydroxy-β-phenethyluridine 、 N³-(S)-(+)-α-hydroxy-β-phenethyluridine
  参考文献：
  名称：

  Metabolism of a novel hypnotic, N³-phenacyluridine, and hypnotic and sedative activities of its enantiomer metabolites in mouse

  摘要：

  1. The metabolism of N-3-phenacyluridine (3-phenacyl-1-beta-D-ribofuranosyluracil), a potent hypnotic nucleoside derivative, was studied in mouse.2. Of the radioactivity, 65 % was excreted in urine within 48 h after intraperitoneal (i.p.) administration of [H-3]N3-phenacyluridine. The urinary metabolites N-3-phenacyluracil and N-3-alpha-hydroxy-beta-phenethyluridine were extracted, isolated and analyzed by mass spectrometry.3. Racemates of N-3-alpha-hydroxy-beta-phenethyluridine were synthesized and both isomers were separated as N-3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine and N-3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine by hplc (CHIRALCEL-OJ column) with retentions of 13.8 and 17.9 min respectively. The reduction process took place with high stereo-selectivity, which pave an alcohol product in the urine with the same retention (17.9 min) as one of the synthetic isomers separated by hplc.4. One of urinary metabolites was identified as N-3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine. N3-phenacyluridine was predominantly converted to an alcoholic metabolite of (S)-(+)-configuration.5. N-3-phenacyluracil and uridine were also identified as minor metabolites.6. The pharmacological effects of the metabolites and related compounds were also evaluated in mouse. N-3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, but not N-3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine, possessed hypnotic activity and potentiated pentobarbital-induced sleeping time with a similar potency to the parent compound, N-3-phenacyluridine. N-3-alpha-hydroxy-beta-phenethyluridine (racemate) had almost two thirds of the hypnotic activity of N-3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine No other metabolites exhibited hypnotic activities.7. The present study indicates that N-3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, a major metabolite of N-3-phenacyluridine, is an active metabolite and contributes a significant CNS depressant effect..

  DOI：

  10.1080/004982500406462

文献信息

• Metabolism of a novel hypnotic, N³-phenacyluridine, and hypnotic and sedative activities of its enantiomer metabolites in mouse
  作者：T. Kimura、M. Miki、K. Watanabe、S. Kondo、I. K. Ho、I. Yamamoto

  DOI：10.1080/004982500406462

  日期：2000.1

  1. The metabolism of N-3-phenacyluridine (3-phenacyl-1-beta-D-ribofuranosyluracil), a potent hypnotic nucleoside derivative, was studied in mouse.2. Of the radioactivity, 65 % was excreted in urine within 48 h after intraperitoneal (i.p.) administration of [H-3]N3-phenacyluridine. The urinary metabolites N-3-phenacyluracil and N-3-alpha-hydroxy-beta-phenethyluridine were extracted, isolated and analyzed by mass spectrometry.3. Racemates of N-3-alpha-hydroxy-beta-phenethyluridine were synthesized and both isomers were separated as N-3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine and N-3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine by hplc (CHIRALCEL-OJ column) with retentions of 13.8 and 17.9 min respectively. The reduction process took place with high stereo-selectivity, which pave an alcohol product in the urine with the same retention (17.9 min) as one of the synthetic isomers separated by hplc.4. One of urinary metabolites was identified as N-3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine. N3-phenacyluridine was predominantly converted to an alcoholic metabolite of (S)-(+)-configuration.5. N-3-phenacyluracil and uridine were also identified as minor metabolites.6. The pharmacological effects of the metabolites and related compounds were also evaluated in mouse. N-3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, but not N-3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine, possessed hypnotic activity and potentiated pentobarbital-induced sleeping time with a similar potency to the parent compound, N-3-phenacyluridine. N-3-alpha-hydroxy-beta-phenethyluridine (racemate) had almost two thirds of the hypnotic activity of N-3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine No other metabolites exhibited hypnotic activities.7. The present study indicates that N-3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, a major metabolite of N-3-phenacyluridine, is an active metabolite and contributes a significant CNS depressant effect..