2',3',5'-tri-O-acetyl-2-thiouridine | 28542-31-6

• 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: 2',3',5'-tri-O-acetyl-2-thiouridine
• 英文别名: 2',3',5'-Tri-O-acetyl-2-thiouridin；O^2'_,O3'_,O5'-triacetyl-2-thio-uridine；(2R,3R,4R,5R)-2-(Acetoxymethyl)-5-(4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3,4-diyl diacetate；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(4-oxo-2-sulfanylidenepyrimidin-1-yl)oxolan-2-yl]methyl acetate
• CAS: 28542-31-6
• 化学式: C₁₅H₁₈N₂O₈S
• 分子量: 386.383
• InChiKey: YKDNCFTUUKOENT-FMKGYKFTSA-N

物化性质

• 密度：
  1.45±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于二氯甲烷、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  153
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2',3',5'-tri-O-acetyl-2-thiouridine 在 劳森试剂 作用下， 以 甲苯 为溶剂， 以83%的产率得到2',3',5'-tri-O-acetyl-2,4-dithiouridine
  参考文献：
  名称：

  Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists

  摘要：

  The phosphate, uracil, and ribose moieties of uracil nucleotides were varied structurally for evaluation of agonist activity at the human P2Y(2), P2Y(4), and P2Y(6) receptors. The 2-thio modi. cation, found previously to enhance P2Y2 receptor potency, could be combined with other favorable modi. cations to produce novel molecules that exhibit high potencies and receptor selectivities. Phosphonomethylene bridges introduced for stability in analogues of UDP, UTP, and uracil dinucleotides markedly reduced potency. Truncation of dinucleotide agonists of the P2Y(2) receptor, in the form of Up(4)-sugars, indicated that a terminal uracil ring is not essential for moderate potency at this receptor and that specific SAR patterns are observed at this distal end of the molecule. Key compounds reported in this study include 9, alpha, beta-methylene-UDP, a P2Y(6) receptor agonist; 30, Up(4)-phenyl ester and 34, Up(4)-[1] glucose, selective P2Y(2) receptor agonists; dihalomethylene phosphonate analogues 16 and 41, selective P2Y(2) receptor agonists; 43, the 2-thio analogue of INS37217 (P-1-(uridine-5')-P-4-(2'-deoxycytidine-5') tetraphosphate), a potent and selective P2Y(2) receptor agonist. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.05.013
• 作为产物：
  描述：

  在 碳酸氢钠 作用下， 以 水 、 1,2-二氯乙烷 为溶剂， 生成 2',3',5'-tri-O-acetyl-2-thiouridine
  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

文献信息

• [EN] MODIFIED NUCLEIC ACID MOLECULES AND USES THEREOF<br/>[FR] MOLÉCULES D'ACIDE NUCLÉIQUE MODIFIÉES ET LEURS UTILISATIONS
  申请人：MODERNA THERAPEUTICS INC

  公开号：WO2014093924A1

  公开（公告）日：2014-06-19

  The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using them.

  本公开提供了经修改的核苷、核苷酸和核酸，以及它们的使用方法。
• 一种核苷磷酸酯及其合成方法与抗肝炎病毒的制药应用
  申请人：南京颐媛生物医学研究院有限公司

  公开号：CN113278041A

  公开（公告）日：2021-08-20

  本发明属于药物化学技术领域，特别涉及一种核苷磷酸酯及其合成方法与抗肝炎病毒的制药应用。本发明核苷磷酸酯为2‑硫代‑N‑羟基胞嘧啶核糖核苷磷酸酯，合成方法路线步骤简洁，产物收率高。本发明通过实验验证，化合物2‑硫代‑N‑羟基胞嘧啶核糖核苷磷酸酯对HepG2.2.15细胞分泌HBV DNA具有良好的抑制作用，具有抗肝炎病毒活性，为治疗病毒性肝炎提供了一种好的选择。
• 2-硫代-N-羟基胞嘧啶核糖核苷磷酸酯及其抗病毒药物用途
  申请人：南京颐媛生物医学研究院有限公司

  公开号：CN114230623B

  公开（公告）日：2022-05-17

  本发明公开了一种2‑硫代‑N‑羟基胞嘧啶核糖核苷磷酸酯，结构式为：，本发明公开的化合物对HepG2.2.15细胞分泌HBV DNA具有良好的抑制作用，具有抗肝炎病毒活性，为治疗病毒性肝炎提供了一种好的选择，对开发更理想的治疗乙肝药物也具有重要意义。
• [EN] ALTERNATIVE NUCLEIC ACID MOLECULES AND USES THEREOF<br/>[FR] MOLÉCULES D'ACIDE NUCLÉIQUE ALTERNATIVES ET LEURS UTILISATIONS
  申请人：MODERNA THERAPEUTICS INC

  公开号：WO2015196130A3

  公开（公告）日：2016-03-03
• Alternative nucleic acid molecules and uses thereof
  申请人：Moderna Therapeutics, Inc.

  公开号：EP2918275B1

  公开（公告）日：2016-05-18