2,3'-anhydro-5'-O-triphenylmethyl-β-(E)-5-(2-bromovinyl)-2'-deoxyuridine | 83894-65-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 2,3'-anhydro-5'-O-triphenylmethyl-β-(E)-5-(2-bromovinyl)-2'-deoxyuridine
• 英文别名: (1R,9R,10R)-4-[(E)-2-bromoethenyl]-10-(trityloxymethyl)-8,11-dioxa-2,6-diazatricyclo[7.2.1.02,7]dodeca-3,6-dien-5-one
• CAS: 83894-65-9
• 化学式: C₃₀H₂₅BrN₂O₄
• 分子量: 557.443
• InChiKey: JTRXQABDYBLMEV-BEYHAKMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,3'-anhydro-5'-O-triphenylmethyl-β-(E)-5-(2-bromovinyl)-2'-deoxyuridine 在 sodium azide 、 对硝基苯酚 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 以79%的产率得到3'-azido-3'-deoxy-5'-O-triphenylmethyl-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
• 作为产物：
  描述：

  在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以351 mg的产率得到2,3'-anhydro-5'-O-triphenylmethyl-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

文献信息

• [EN] PROTEIN STABILIZING COMPOUNDS CONTAINING USP7 LIGANDS<br/>[FR] COMPOSÉS DE STABILISATION DE PROTÉINE CONTENANT DES LIGANDS D'USP7
  申请人：STABLIX INC

  公开号：WO2022272133A3

  公开（公告）日：2023-02-09
• 3′-[4-Aryl-(1,2,3-triazol-1-yl)]-3′-deoxythymidine Analogues as Potent and Selective Inhibitors of Human Mitochondrial Thymidine Kinase
  作者：Sara Van Poecke、Ana Negri、Federico Gago、Ineke Van Daele、Nicola Solaroli、Anna Karlsson、Jan Balzarini、Serge Van Calenbergh

  DOI：10.1021/jm901532h

  日期：2010.4.8

  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.