3D-QSAR Study on the Influence of Alrylamino (R) Substituents on Herbicidal Activity of Thiourea Analogues

Abstract

Influences of alrylamino (R) substituents on the herbicidal activity (<TEX>$pI_{50}$</TEX>) of 1-(4-chloro-2-fluoro-5-propargyloxypheny)-3-(R)-thiourea analogues (1 ~ 35) against the barnyard grass (Echinochloa crusgalli) in the pre-emergence step were discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) as the three dimensional quantitative structure-activity relationship (3D-QSAR) method. The statistically most satisfactory CoMFA models for the herbicidal activity against the barnyard grass had the better predictability (<TEX>$r^2{_{cv.}}$</TEX>) and correlativity (<TEX>$r^2{_{ncv.}}$</TEX>) than those of CoMSIA models. The optimized CoMFA model 1(<TEX>$r^2{_{cv.}}$</TEX> = 0.531 & <TEX>$r^2{_{ncv.}}$</TEX> = 0.931) with the sensitivity to the perturbation (<TEX>${d_q}^{2'}{dr^2}_{yy'}$</TEX> = 1.081) and the prediction (<TEX>$q^2$</TEX> = 0.475) produced by a progressive scrambling analyses were not dependent on chance correlation. And statistical qualities with the atom based fit alignment (AF) were slightly higher than those of the field fit alignment (FF). According to the optimized CoMFA model 1, the contribution ratio (%) of the steric field (76.9%) on the herbicidal activity of the Thioureas was three-fold higher than that of the electrostatic field (20.1%) and the hydrophobic field (3.0%) had the least influence. A steric favor group is on the vicinity of the nitrogen atom in alrylamino (R) substituent, and a steric disfavor group is on the outer side of alrylamino (R) substituent. Thus, as the size of alrylamino (R) substituent increases, so does the herbicidal activity of the substituent.