52980-49-1Relevant academic research and scientific papers
Quantitative structure activity relationship of reversible dihydrofolate reductase inhibitors. Diaminotriazines
Hansch,Silipo
, p. 661 - 667 (1974)
A quantitative structure activity relationship (QSAR) has been formulated for 4,6 diamino 1,2 dihydro 2,2 dimethyl 1 (X phenyl) s triazines inhibiting dihydrofolate reductase, isolated from Walker 256 tumor. Using substituent constants and regression analysis, it is shown that the substituents X on the phenyl ring are placed into two different types of space in, or on, the enzyme. Substituents in the 3 position show typical hydrophobic interaction while substituents in the 4 position bring about inhibition in a fashion more closely related to their molecular volume as characterized by molecular refractivity. The electronic effects of X as measured by sigma do not appear to have a significant role. The QSAR for 83 inhibitors is described by log 1/C = 0.89(π-3) + 0.15(MR-4) - 0.13(π-3)2 + 6.62, where π-3 is the hydrophobic effect of substituents in the 3 position, and MR-4 is the molecular refractivity of 4 substituents. The correlation coefficient for this equation is 0.905. The design of better inhibitors is discussed in the light of the above equation.
