Quantitative structure-activity relationship study on some dihydropteridine reductase inhibitors.
The dihydropteridine reductase (DHPR) inhibitory potencies of some 4-phenyltetrahydropyridines, 4-phenylpiperidines, and 4-phenylpyridines, are analyzed in relation to their physico-chemical and molecular properties. They are found to have significant correlation with Hammett constant sigma and the van der Waals volume Vw. The correlation is linear with sigma and parabolic with Vw. 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.
Babbar
R
R
Department of Chemistry, Birla Institute of Technology and Science, Pilani, India.
Gupta
J K
JK
Gupta
S P
SP
D004093:Dihydropteridine Reductase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008433:Mathematics; D015394:Molecular Structure; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D010880:Piperidines; D011725:Pyridines; D004093:Dihydropteridine Reductase; D009247:NADH, NADPH Oxidoreductases