P. Babczinski, M. Blunck, G. Sandmann
May 1, 1995
Citations
0
Influential Citations
18
Citations
Journal
Pesticide Biochemistry and Physiology
Abstract
Abstract Substituted phenyltetrahydropyrimidinones (so-called cyclic ureas) are new chlorosis-inducing preemergence herbicides inhibiting carotenoid biosynthesis at the phytoene desaturase step. Using 138 compounds, structure-activity investigations with either greenhouse data (growth in soil under paddy conditions) or biochemical parameters (phytoene accumulation, loss of carotenoids) from cress seedling grown in vermiculite demonstrate the type of substitution in the general structure I favorable for herbicidal and carotenoid biosynthesis inhibitory activity. Both N-linked ligands should be phenyl and at least one substituent on one phenyl ring is essential. This substitution must be at the meta position. The highest activity is obtained with -CF 3 followed by -Cl, -Br, or -SCH 3 , whereas carbonylic and NO 2 substituents yield poor results. 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 meta position in order to maintain activity. Cyclization of the central urea moiety to a six-member ring gives the best inhibitors, whereas five- or seven-member cyclic ureas are less effective. The optimum element for X in I is 2-methyl-1,3-propylen, giving a 5-methyltetrahydropyrimidine-2-one. The unmethylated compound with X = 1,3-propylen is either 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-diphenyl-5-methyl-(4 H )-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 biological parameter (carotenoid formation by cress seedlings) was described by certain increments for substituent modifications. The inclusion of a quadratic term for the lipophilicity parameter R m into the model equation considerably improves the fit between experimental and calculated values, indicating a nonlinear dependence of the biological activity on the lipophilicity of the compounds.