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Design, synthesis and enzymatic evaluation of 6-bridged imidazolyluracil derivatives as inhibitors of human thymidine phosphorylase
- Source :
- The Journal of pharmacy and pharmacology. 59(4)
- Publication Year :
- 2007
-
Abstract
- A series of novel imidazolyluracil conjugates were rationally designed and synthesised to probe the active site constraints of the angiogenic enzyme, thymidine phosphorylase (TP, E.C. 2.4.2.4). The lead compound in the series, 15d, showed good binding in the active site of human TP with an inhibition in the low μM range. The absence of a methylene bridge between the uracil and the imidazolyl sub-units (series 16) decreased potency (up to 3-fold). Modelling suggested that active site residues Arg202, Ser217 and His116 are important for inhibitor binding.
- Subjects :
- Models, Molecular
Stereochemistry
Pharmaceutical Science
Methylene bridge
chemistry.chemical_compound
Inhibitory Concentration 50
Structure-Activity Relationship
Potency
Humans
Thymidine phosphorylase
Enzyme Inhibitors
Uracil
Pharmacology
chemistry.chemical_classification
Thymidine Phosphorylase
Binding Sites
biology
Chemistry
Active site
Combinatorial chemistry
Enzyme
Drug Design
biology.protein
Lead compound
Conjugate
Subjects
Details
- ISSN :
- 00223573
- Volume :
- 59
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- The Journal of pharmacy and pharmacology
- Accession number :
- edsair.doi.dedup.....4e041fc8b8b61bb9d03f56a10c958cac