The following conclusion was made from the 2D-QSAR model for the tyrosinase inhibitory activity according to the variation of the substituents R 1 and R 2 in analogues of compound 2-[(2,6-dioxocyclohexyl)methyl]cyclohexane-1,3-dione (1-23). The best optimized 2D-QSAR model was Obs.pI 50 = -0.295 (± 0.031)TDM -0.120 (± 0.014 )DMZ + 0.135 (± 0.050)DMX. R 2 + 6.382 (± 0.17), and the correlation (r 2 = 0.905) of which was greater than its predictability (q 2 = 0.843). The magnitude of the effect of tyrosinase inhibitory activities was in order of TDM > DMX.R 2 ≥ DMZ, and it tended to increase as the hydrophobicity of substrate molecule (ClogP > 0) as well as the steric favor of substituent R 1 increased. The analysis of the model implies that inhibitory activity of substrate molecule will increase as DMX.R 2 (Dipole moment X component of R 2 -substituent) increases, while TDM (Total Dipole Moment) and DMZ
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