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 | 144405-50-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 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
• 英文名称: N³-phenacyluridine
• 英文别名: 3-phenacyl-1-β-D-ribofuranosyluracil；N(3)-Phenacyluridine；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3-phenacylpyrimidine-2,4-dione
• CAS: 144405-50-5
• 化学式: C₁₇H₁₈N₂O₇
• 分子量: 362.339
• InChiKey: ABVJRGKUSBWHJY-DTZQCDIJSA-N

物化性质

• 沸点：
  633.8±65.0 °C(Predicted)
• 密度：
  1.523±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  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， 以60.4%的产率得到N³-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
• 作为产物：
  描述：

  alpha-氯乙酰苯 、 尿嘧啶核苷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 4.0h， 以82%的产率得到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
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Uracil Nucleotide Derivatives and Analogues as Agonists at Human P2Y₂, P2Y₄, and P2Y₆ Receptors

  摘要：

  A series of UTP, UDP, and UMP derivatives and analogues were synthesized and evaluated at the human pyrimidinergic P2Y receptor subtypes P2Y(2), P2Y(4), and P2Y(6) stably expressed in 1321N1 astrocytoma cells. Substituents at N3 of UTP were poorly tolerated by P2Y2 and P2Y4 receptors. In contrast, a large phenacyl substituent at N3 of UDP was well tolerated by the P2Y6 receptor, yielding a potent and selective P2Y6 receptor agonist (3-phenacyl-UDP, EC50 = 70 nM, > 500-fold selective). The most potent and selective P2Y2 receptor agonist of the present series was 2-thio-UTP (EC50 = 50 nM, >= 30-fold selective vs P2Y(4) and P2Y6). All modifications at the uracil base of UTP led to a decrease in potency at the P2Y4 receptor. A beta,gamma-dichloromethylene modification in the triphosphate chain of 5-bromo-UTP was tolerated by all three receptor subtypes, thus opening up a new strategy to obtain ectonucleotide diphosphohydrolase- and phosphatase-resistant P2Y(2), P2Y(4), and P2Y(6) receptor agonists.

  DOI：

  10.1021/jm060848j

文献信息

• Proteins and nucleic acids encoding same
  申请人：——

  公开号：US20040005576A1

  公开（公告）日：2004-01-08

  Disclosed are polypeptides and nucleic acids encoding same. Also disclosed are vectors, host cells, antibodies and recombinant methods for producing the polypeptides and polynucleotides, as well as methods for using same.

  公开了多肽和编码多肽的核酸。还公开了生产多肽和多核苷酸的载体、宿主细胞、抗体和重组方法，以及使用它们的方法。
• Structural Modifications of UMP, UDP, and UTP Leading to Subtype-Selective Agonists for P2Y₂, P2Y₄, and P2Y₆ Receptors
  作者：Ali El-Tayeb、Aidong Qi、Robert A. Nicholas、Christa E. Müller

  DOI：10.1021/jm1016297

  日期：2011.4.28

  A large series of derivatives and analogues of the uracil nucleotides UMP, UDP, and UTP with modifications in various positions of the uracil moiety and/or the phosphate groups were synthesized and evaluated at human P2Y(2), P2Y(4), and P2Y(6) receptors. 2-(Ar)alkylthio substitution of UMP and UDP was best tolerated by the P2Y(2) receptor, 2-Phenethylthio-UMP (13e) showed an EC50 value of 1.3 mu M at P2Y(2) and > 70-fold selectivity versus P2Y(4) and P2Y(6) receptors. Substitution of the 2-keto group in UMP by NH (13g, iso-CMP) resulted in the first potent and selective P2Y(4) agonist (EC50 4.98 mu M > 20-fold selective vs P2Y(2) and P2Y(6)). In contrast, :replacement of the 2-keto function in UDP by NH yielded a potent P2Y(2) agonist (12g, iso-CDP, EC50 = 0.604 mu M, > 100-fold selective). In an attempt to obtain metabolically stable UTP analogues, beta,gamma-dichloro- and beta,gamma-difluoro-methylene-UTP derivatives were synthesized. The triphosphate modifications were much better tolerated by P2Y(2), and in some cases also by P2Y(6), than by P2Y(4) receptors. 4-Thio-beta,gamma-difluoromethylene-UTP (14g) was a potent P2Y(2) agonist with an EC50 value of 0.134 mu M and > 50-fold selectivity. N3-Phenacyl-beta,gamma-dichloromethylene-UTP (14b) proved to be a potent P2Y(6) receptor agonist (EC50 0.142 mu M) with high selectivity versus P2Y(4) (50-fold) and moderate selectivity versus P2Y(2) receptors (6-fold).
• PUTATIVE PROTEINS AND NUCLEIC ACIDS ENCODING SAME
  申请人：Curagen Corporation

  公开号：EP1366162A2

  公开（公告）日：2003-12-03
• JPH0559087A
  申请人：——

  公开号：JPH0559087A

  公开（公告）日：1993-03-09
• US7045509B2
  申请人：——

  公开号：US7045509B2

  公开（公告）日：2006-05-16