6-phenylthiouridine | 85451-50-9

• 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: 6-phenylthiouridine
• 英文别名: 6-(Phenylthio)uridine；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-phenylsulfanylpyrimidine-2,4-dione
• CAS: 85451-50-9
• 化学式: C₁₅H₁₆N₂O₆S
• 分子量: 352.368
• InChiKey: HTYSYCYYXOXEKS-ICGCDAGXSA-N

物化性质

• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-phenylthiouridine 在 磷酸三甲酯 、 三氯氧磷 作用下， 反应 6.0h， 生成 6-phenylthiouridine 5'-phosphate
  参考文献：
  名称：

  The reaction of 6-phenylthiouridine with sulfur nucleophiles: A simple and regiospecific preparation of 6-alkylthiouridines and 6-alkylthiouridylic acids.

  摘要：

  通过一个区域特异性亲核反应，从相应的 6-苯基硫依啶衍生物合成了 6-烷基硫依啶和 6-烷基硫依啶酸。

  DOI：

  10.1248/cpb.31.1222
• 作为产物：
  描述：

  2',3'-O-isopropylidene-5'-O-methoxy-methyl-6-phenylthiouridine 在 三氟乙酸 作用下， 以 水 为溶剂， 以77%的产率得到6-phenylthiouridine
  参考文献：
  名称：

  “ Umpulong”在尿苷C-6位的反应性：6-取代尿苷的简单通用方法

  摘要：

  发现锂化的2'，3'-O-异丙基-5'-甲氧基甲基-尿苷与多种亲电试剂在C-6位置上区域特异性地反应。在温和条件下用三氟乙酸水溶液同时除去6-官能化产物中核糖部分的保护基。因此，本发明方法可以简单且通用地合成6-取代的尿苷。

  DOI：

  10.1016/0040-4020(82)80016-1

文献信息

• Synthesis and biological activities of 5-substituted 6-phenylthio and 6-iodouridines, a new class of antileukemic nucleosides.
  作者：Hiromichi Tanaka、Akira Matsuda、Shuji Iijima、Hiroyuki Hayakawa、Tadashi Miyasaka

  DOI：10.1248/cpb.31.2164

  日期：——

  A new class of 5, 6-disubstituted uridines, in which the C-6 position was occupied by phenylthio group or iodine, were synthesized via lithiation of the corresponding 5-substituted 2', 3'-O-isopropylidene-5'-O-methoxymethyluridines and subsequent electrophilic reactions. These newly-synthesized uridine derivatives exhibited antileukemic activities against mouse leukemia L5178Y cells in culture.

  合成了一类新的5, 6-二取代尿苷，其中C-6位点被苯硫基或碘取代，通过相应5-取代的2', 3'-O-异丙烯基-5'-O-甲氧甲基尿苷的锂化及后续的电亲核反应进行合成。这些新合成的尿苷衍生物在培养中表现出对小鼠白血病L5178Y细胞的抗白血病活性。
• 5-OMe-UDP is a Potent and Selective P2Y₆-Receptor Agonist
  作者：Tamar Ginsburg-Shmuel、Michael Haas、Marlen Schumann、Georg Reiser、Ori Kalid、Noa Stern、Bilha Fischer

  DOI：10.1021/jm901450d

  日期：2010.2.25

  P2Y nucleotide receptors (P2Y-Rs) play Important physiological roles. However, most of the P2Y-R subtypes are still lacking potent and selective agonists and antagonists. Based on data mining analysis of binding interactions in 44 protein-uridine nucleos(t)ides complexes, we designed uracil nucleotides, substituted at the C5/C6 position. All C6-substituted derivatives were inactive at the P2Y(2,4,6)-Rs, while out of the C5-substituted analogues, only 5-OMe-UD(T)P showed activity. To rationalize the data, the ionization and conformation of these analogues were evaluated. The pK(a) values of most analogues Substituted at the C5/C6 positions were unaltered compared to UTP (pK(a) 9.42), except for 5-F-UTP nucleotide (pK(a) 7.85). C6-substituted analogues adopt the syn or high-syn conformations, which are disfavored by the receptors, while 5-OMe-UD(T)P adopt the favored anti. conformation. Furthermore, 5-OMe-UDP adopts the S sugar puckering, which is the conformation preferred by the P2Y(6)-R, but not the P2Y(2)- or P2Y(4)-Rs. 5-OMe-UDP fulfills the conformational and H-bonding requirements of P2Y(6)-R, thus, making a potent P2Y(6)-R agonist (EC50 0.08 mu M), more than UDP (EC50 0.14 mu M).