Quantitative Structure-Activity Relationship Study on Some Dihydropteridine Reductase Inhibitors

Abstract

The dihydropteridine reductase (DHPR) inhibitory potencies of some 4-phenyltetrahydropyridines, 4-phenylpiperidines, and 4-phenylpyridines, are analyzed in relation to their physicochemical and molecular properties. They are found to have significant correlation with Hammett constant s and the van der Waals volume V_w. The correlation is linear with s and parabolic with V_w. Hence, it is argued that DHPR inhibition involves dispersion interaction and is enhanced by electron donation from the substituents but hindered by steric effects produced by large substituents. It is also found that these electronic and steric effects are significant only when they are produced by substituents being at specific position in the molecules.

Key Words: :

• Dihydropteridine reductase inhibitors
• 4-phenylpiperidines
• 4-phenylpyridines
• 4-phenyltetrahydropyridines
• quantitative structure-activity relationship study