1439-10-7Relevant articles and documents
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 (2004)
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.
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.
Bromination of Some Pyridine and Diazine N-Oxides
Paudler, William W.,Jovanovic, Misa V.
, p. 1064 - 1069 (2007/10/02)
Selected monosubstituted pyridines, pyrazines, pyrimidines, and their N-oxides, having an electron-donating substituent, were successfully brominated under very mild conditions.The N-oxide function itself is not sufficient to cause these ?-deficient systems to undergo electrophilic aromatic halogenation.Only strongly electron-donating substituents (amino groups) activate the heterocyclic nucleus toward bromination.These substituents direct the electrophilic substitution ortho/para to them with or without the N-oxide group present.Pyridine and diazines with moderately activating substituents such as alkoxy groups are brominated only when their ortho/para activation is augmented by the activation of the N-oxide funtion.Failure to brominate 5-methoxypyrimidine 1-oxide may well reflect the greater ? deficiency of the pyrimidine ring.
