SUBSTITUTED TETRAHYDROPYRIMIDINONES - A NEW HERBICIDAL CLASS OF COMPOUNDS INDUCING CHLOROSIS BY INHIBITION OF PHYTOENE DESATURATION .2. STRUCTURE-ACTIVITY-RELATIONSHIPS

Substituted phenyltetrahydropyrimidinones (so-called cyclic ureas) are new chlorosis-inducing preemergence herbicides inhibiting carotenoid biosynthesis at the phytoene desaturase step. Using 138 compounds, str ucture-activity investigations with either greenhouse data (growth in soil under paddy conditions) or biochemical parameters (phytoene accum ulation, loss of carotenoids) from cress seedling grown in vermiculite demonstrate the type of substitution in the general structure I favor able for herbicidal and carotenoid biosynthesis inhibitory activity. B oth N-linked ligands should be phenyl and at least one substituent on one phenyl ring is essential. This substitution must be at the meta po sition. The highest activity is obtained with -CF3 followed by -Cl, -B r, or -SCH3, whereas carbonylic and NO2 substituents yield poor result s. Obviously, meta-substituents with high lipophilicity combined with electron-withdrawing properties are favorable for activity. Additional substitution at the same phenyl ring is allowed only at the other met a position in order to maintain activity. Cyclization of the central u rea moiety to a six-member ring gives the best inhibitors, whereas fiv e- or seven-member cyclic ureas are less effective. The optimum elemen t for X in I is 2-methyl-1,3-propylen, giving a 5-methyltetrahydropyri midine-2-one. The unmethylated compound with X = 1,3-propylen is eithe r evenly or slightly less active (depending on the phenyl substitution ) but ranks better than the 6-methylated or 5-dimethylated derivative. For 47 derivatives modified at various positions of the basic 1,3-dip henyl-5-methyl-(4H)-pyrimidine-2-one molecule a quantitative structure -activity relationship was calculated according to an extended Fujita- Ban model. Linear regression equations were obtained in which the biol ogical parameter (carotenoid formation by cress seedlings) was describ ed by certain increments for substituent modifications. The inclusion of a quadratic term for the lipophilicity parameter R(m) into the mode l equation considerably improves the fit between experimental and calc ulated values, indicating a nonlinear dependence of the biological act ivity on the lipophilicity of the compounds. (C) 1995 Academic Press, Inc.