Structural Effects ofN-Arylcarbamoylpyrazolines on Calcium Uptake in Rat Brain Synaptosomes

Abstract

N-Arylcarbamoylpyrazolines with various substituents at the para position of the carbamoyl benzene ring inhibited ATP-dependent Ca 2+ -uptake in synaptosomes prepared from the rat brain. The activity of these compounds was evaluated as log(1/I 50 ), the reciprocal logarithm of half inhibitory concentration, I 50 (M), from the concentration-response curve for the inhibition of Ca 2+ -uptake. Among the compounds tested, methyl 3-(4-chlorophenyl)-4-methyl-1-[N-(4-trifluoromethylphenyl)carbamoyl]-2-pyrazoline-4-carboxylate was the most potent, the I 50 value of which as 9.12 x 10 -7 M. Variations in the activity in terms of log(1/I 50 ) were quantitatively analysed using a substituent parameter, showing that the higher the electron-withdrawing effect of the substituent, the higher was the activity. The substituent effects were similar to those on insecticidal activity against the American cockroach. The higher the inhibitory activity against Ca 2+ uptake, the higher seemed to be the insecticidal activity. Methyl (4S)-3-(4-chlorophenyl)-4-methyl-1-[N-(4-chlorophenyl)carbamoyl]-2-pyrazoline-4-carboxylate had higher inhibitory activity against Ca 2+ -uptake and higher insecticidal activity than the R-isomer, but the difference was greater in the Ca 2+ -uptake system.