3'-(4-chlorophenyl-1,2,3-triazol-1-yl)-3'-deoxy-β-(E)-5-(2-bromovinyl)-2'-deoxyuridine | 1219808-54-4

• 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: 3'-(4-chlorophenyl-1,2,3-triazol-1-yl)-3'-deoxy-β-(E)-5-(2-bromovinyl)-2'-deoxyuridine
• 英文别名: 5-[(E)-2-bromoethenyl]-1-[(2R,4S,5S)-4-[4-(4-chlorophenyl)triazol-1-yl]-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 1219808-54-4
• 化学式: C₁₉H₁₇BrClN₅O₄
• 分子量: 494.732
• InChiKey: MNYPSYJHVXNBMF-CGXZTUQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯苯乙炔 、 3'-azido-3'-deoxy-β-(E)-5-(2-bromovinyl)-2'-deoxyuridine 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 24.25h， 以6%的产率得到3'-(4-chlorophenyl-1,2,3-triazol-1-yl)-3'-deoxy-β-(E)-5-(2-bromovinyl)-2'-deoxyuridine
  参考文献：
  名称：

  3′-[4-Aryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidine Analogues as Potent and Selective Inhibitors of Human Mitochondrial Thymidine Kinase

  摘要：

  In an effort to increase the potency and selectivity of earlier identified substrate-based inhibitors of mitochondrial thymidine kinase 2 (TK-2), we now describe the synthesis of new thymidine analogues containing a 4- or 5-substituted 1,2,3-triazol-1-yl substituent at the 3'-position of the 2'-deoxyribofuranosyl ring. These analogues were prepared by Cu- and Ru-catalyzed cycloadditions of 3'-azido-3'-deoxythymidine and the appropriate alkynes, which produced the 1,4- and 1,5-triazoles, respectively. Selected analogues showed nanomolar inhibitory activity for TK-2, while virtually not affecting the TK-1 counterpart. Enzyme kinetics indicated a competitive and uncompetitive inhibition profile against thymidine and the cosubstrate ATP, respectively. This behavior is rationalized by suggesting that the inhibitors occupy the substrate-binding site in a TK-2 ATP complex that maintains the enzyme's active site in a closed conformation through the stabilization of a small lid domain.

  DOI：

  10.1021/jm901532h