Abstract
The biochemical role of dihydrofolate reductase (DHFR) (EC 1.5.1.3)is discussed, together with the role of tetrahydrofolate in intermediary cellular metabolism. The development of classical folate analogues and non-classical, small molecule inhibitors, and some of the problems associated with their use in cancer chemotherapy is reviewed.
The novel lipophilic inhibitor of DHFR, methylbenzaprim, is the
parent compound from which a series of analogues were synthesised. The preparative route to formation of these analogues involved the aromatic nucleophilic substitution of a series of substituted
benzylamines onto m-nitropyrimethamine. The possibility of the preparation of an azido-substituted analogue of methylbenzaprim was also investigated...
Date of Award | Jun 1988 |
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Original language | English |
Awarding Institution |
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Keywords
- dihydrofolate reductase
- Dihydrofolate reductase inhibitors