792909-14-9Relevant academic research and scientific papers
Xanthine oxidase-activated prodrugs of thymidine phosphorylase inhibitors
Reigan, Philip,Gbaj, Abdul,Stratford, Ian J.,Bryce, Richard A.,Freeman, Sally
, p. 1248 - 1260 (2008/09/21)
Thymidine phosphorylase (TP) is over-expressed in various tumour types and plays an important role in tumour angiogenesis, growth, invasion and metastasis. The enzymatic activity of TP is required for the angiogenic effect of TP, therefore, inhibitors of TP are of significant interest in cancer chemotherapy. A series of xanthine oxidase (XO) activated prodrugs of known inhibitors of TP have been designed and synthesized with the ultimate intent of improving tumour selectivity and pharmacokinetic characteristics. These prodrugs were not inhibitors of TP, but were selectively oxidized by XO at C-2 and/or C-4 of the uracil ring moiety to generate the desired TP inhibitor. Molecular modelling of both the TP inhibitors and XO-activated prodrugs rationalized their binding in the active site of the human TP crystal structure.
Synthesis and enzymatic evaluation of xanthine oxidase-activated prodrugs based on inhibitors of thymidine phosphorylase
Reigan, Philip,Gbaj, Abdul,Chinje, Edwin,Stratford, Ian J.,Douglas, Kenneth T.,Freeman, Sally
, p. 5247 - 5250 (2007/10/03)
A series of xanthine oxidase-activated prodrugs of known inhibitors of thymidine phosphorylase are described. These prodrugs were oxidised by xanthine oxidase at C-2 and/or C-4 of the uracil ring to generate the desired TP inhibitor. The scheme shows the prodrug of TPI. A series of xanthine oxidase-activated prodrugs of known inhibitors of thymidine phosphorylase has been designed and synthesised to introduce tumour selectivity. These prodrugs were oxidised by xanthine oxidase at C-2 and/or C-4 of the uracil ring to generate the desired TP inhibitor.
