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Inhibition of human dihydrofolate reductase by 2,4-diaminoquinazolines bearing simple substituents on the aromatic ring
- Source :
- Journal of Heterocyclic Chemistry. 28:1981-1986
- Publication Year :
- 1991
- Publisher :
- Wiley, 1991.
-
Abstract
- A series of thirty eight 2,4-diaminoquinazolines having diverse substitution patterns on the aromatic ring was evaluated for inhibitory activity against dihydrofolate reductase (DHFR) obtained from a human lymphoblast cell line. Many of these compounds were also evaluated as inhibitors of rat liver DHFR under the same experimental conditions. In most instances the results obtained with each enzyme were comparable indicating that the rodent enzyme is a suitable model for the human DHFR as far as the determination of I50 values is concerned. The results demonstrate that relatively simple 5-substituted- or 5,6-disubstituted-2,4-diaminoquinazolines can be potent DHFR inhibitors. The presence of a nonpolar substituent at position 7 or 8 was highly detrimental to inhibitory potency.
Details
- ISSN :
- 19435193 and 0022152X
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Journal of Heterocyclic Chemistry
- Accession number :
- edsair.doi...........4a911aef0211e778130d5d5642f0b8cd