2-methylthio-1-(β-D-ribofuranosyl)-4-pyrimidinone | 175875-32-8

• 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: 2-methylthio-1-(β-D-ribofuranosyl)-4-pyrimidinone
• 英文别名: 2-S-Methyl-2-thio-uridin；2-methylthio-1-β-D-ribofuranosyl-pyrimidine-4-one；2-methylsulfanyl-1-β-D-ribofuranosyl-1H-pyrimidin-4-one；S-methyl-2-thio-uridine；Rjmkjbwbwugxed-zoquxtdfsa-；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-methylsulfanylpyrimidin-4-one
• CAS: 175875-32-8
• 化学式: C₁₀H₁₄N₂O₅S
• 分子量: 274.298
• InChiKey: RJMKJBWBWUGXED-ZOQUXTDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-methylthio-1-(β-D-ribofuranosyl)-4-pyrimidinone 在 水 、 三乙基碳酸氢铵缓冲液 、 1,8-双二甲氨基萘 、 三氯氧磷 作用下， 以 磷酸三乙酯 为溶剂， 反应 6.0h， 生成 2-methylthio-UMP
  参考文献：
  名称：

  Structural Modifications of UMP, UDP, and UTP Leading to Subtype-Selective Agonists for P2Y₂, P2Y₄, and P2Y₆ Receptors

  摘要：

  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).

  DOI：

  10.1021/jm1016297
• 作为产物：
  描述：

  [(2R,3R,4R,5R)-3,4-diacetyloxy-5-(2-methylsulfanyl-4-oxopyrimidin-1-yl)oxolan-2-yl]methyl acetate 在 氨 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以40%的产率得到2-methylthio-1-(β-D-ribofuranosyl)-4-pyrimidinone
  参考文献：
  名称：

  Synthesis of S2-Alkyl-2-thiouridines

  摘要：

  5-取代的S 2-烷基-2-硫脲嘧啶1a-i与1,1,1,3,3,3-六甲基二硅氮烷和硫酸铵在回流温度下反应，然后在乙腈中与1,2,3,5-四-O-乙酰基-β-D-核呋喃糖缩合，使用三甲基硅基三氟甲磺酸作为催化剂，得到相应的保护核苷2a-i，这些核苷随后用甲醇中的饱和氨进行去保护。当核碱基在5位上被乙氧羰基或氰基取代或不取代时，核苷的去保护反应也会导致甲硫基团的替换。对于5-烷基和5-甲氧基取代基，则没有观察到这种现象。

  DOI：

  10.1055/s-1996-4187

文献信息

• Sayed Ahmed, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1996, vol. 35, # 6, p. 595 - 597
  作者：Sayed Ahmed

  DOI：——

  日期：——
• Synthesis of S2-Alkyl-2-thiouridines
  作者：Adel A.-H. Abdel-Rahman、Magdy A. Zahran、Ahmed E.-S. Abdel-Megied、Erik B. Pedersen、Claus Nielsen

  DOI：10.1055/s-1996-4187

  日期：1996.2

  5-Substituted S 2-alkyl-2-thiouracils 1a-i were treated with 1,1,1,3,3,3-hexamethyldisilazane and ammonium sulfate at reflux temperature and condensed with 1,2,3,5-tetra-O-acetyl-β-D-ribufuranose in acetonitrile using trimethylsilyl trifluoromethanesulfonate as a catalyst to afford the corresponding protected nucleosides 2a-i which were deprotected with saturated ammonia in methanol. When the nucleobase was substituted with ethoxycarbonyl or cyano groups in the 5-position or was unsubstituted, the deprotection reaction of the nucleoside also resulted in replacement of the methylthio group. This was not observed with 5-alkyl and 5-methoxy substituents.

  5-取代的S 2-烷基-2-硫脲嘧啶1a-i与1,1,1,3,3,3-六甲基二硅氮烷和硫酸铵在回流温度下反应，然后在乙腈中与1,2,3,5-四-O-乙酰基-β-D-核呋喃糖缩合，使用三甲基硅基三氟甲磺酸作为催化剂，得到相应的保护核苷2a-i，这些核苷随后用甲醇中的饱和氨进行去保护。当核碱基在5位上被乙氧羰基或氰基取代或不取代时，核苷的去保护反应也会导致甲硫基团的替换。对于5-烷基和5-甲氧基取代基，则没有观察到这种现象。
• 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).