Quantitative structure-activity relationship by distance geometry: quinazolines as dihydrofolate reductase inhibitors
- 1 August 1982
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 25 (8), 892-899
- https://doi.org/10.1021/jm00350a003
Abstract
Quinazoline inhibitors (68) of dihydrofolate reductase were studied. The binding data fitted to an 11-point model of the site, but improved computer algorithms resulted in a much better overall fit (r 0.95, SD 0.727 kcal) and a more accurate fit for some very loosely bound 2,4-diaminoquinazolines. Removal of 2 of the site points (numbers 5 and 9) gave an even better fit than the original 11 site points. Deleting a 3rd site point (number 8) worsened the calculated binding energies of the loosely bound 2,4-diaminoquinazolines. The results led to predictions of chemical modifications of the quinazolines that should improve their biological activity.This publication has 7 references indexed in Scilit:
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