Inhibition of chicken liver dihydrofolate reductase by 5-(substituted benzyl)-2,4-diaminopyrimidines. A quantitative structure-activity relationship and graphics analysis.
The inhibition of chicken liver dihydrofolate reductase by a series of substituted benzylpyrimidines has been investigated. From the inhibition constants a quantitative structure-activity relationship has been formulated. This mathematical model is compared with molecular graphics models constructed from the X-ray crystallographic coordinates of trimethoprim and 5-(3,4-dimethoxy-4-isopropenylbenzyl)-2,4- diaminopyrimidine bound to the enzyme. There is good correspondence between the two types of models.
Selassie
C D
CD
Fang
Z X
ZX
Li
R L
RL
Hansch
C
C
Klein
T
T
Langridge
R
R
Kaufman
B T
BT
D000818:Animals; D002645:Chickens; D003461:Crystallography; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005493:Folic Acid Antagonists; D008099:Liver / Q000201:enzymology*; D008433:Mathematics; D008958:Models, Molecular; D011743:Pyrimidines / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014295:Trimethoprim / Q000494:pharmacology; D014961:X-Ray Diffraction
D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D011743:Pyrimidines; C031792:2,4-diamino-5-benzylpyrimidine; D014295:Trimethoprim