On the structure selectivity problem in drug design. A comparative study of benzylpyrimidine inhibition of vertebrate and bacterial dihydrofolate reductase via molecular graphics and quantitative structure-activity relationships.
Article Details
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Selassie CD, Fang ZX, Li RL, Hansch C, Debnath G, Klein TE, Langridge R, Kaufman BT
On the structure selectivity problem in drug design. A comparative study of benzylpyrimidine inhibition of vertebrate and bacterial dihydrofolate reductase via molecular graphics and quantitative structure-activity relationships.
J Med Chem. 1989 Aug;32(8):1895-905.
- PubMed ID
- 2502631 [ View in PubMed]
- Abstract
Quantitative structure-activity relationships (QSAR) have been derived for the action of 68 5-(substituted benzyl)-2,4-diaminopyrimidines on dihydrofolate reductase (DHFR) from Lactobacillus casei and chicken liver. The QSAR are analyzed with respect to the stereographics models of the active sites of the enzymes and found to be in good agreement. Using these QSAR equations, we have attempted to design new trimethoprim-type antifolates having higher selectivity for the bacterial enzyme. The general problem of developing selective inhibitors is discussed.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Trimethoprim Dihydrofolate reductase Ki (nM) 131.83 N/A N/A Details Trimethoprim Dihydrofolate reductase Ki (nM) 104712.85 N/A N/A Details