PHYSICOCHEMICAL PARAMETERS INVOLVED IN THE LETHAL TOXICITY OF N,N-[(DIMETHYLAMINO)ETHYL]-4-SUBSTITUTED BENZOATE HYDROCHLORIDES - A QSAR STUDY

A set of sixteen para-substituted N,N-[(dimethylamino)ethyl] benzoate hydrochlorides structurally related to procaine was synthesized. The a pparent partition coefficients were determined by either shake-flask o r HPLC methods and were taken as hydrophobic parameters. The IR stretc hing frequencies of the carbonyl group were determined in chloroform a nd taken as one of the electronic parameters. Additional physicochemic al parameters were either taken from the literature: pi, sigma, T and R, MR4, or calculated: log P. The lethal potency was determined in the mouse via the LD50. In order to verify the nature and the relative co ntributions of the physicochemical parameters to lethal toxicity, QSAR equations were derived using regression analysis. A major contributio n of hydrophobicity to ether with a smaller but still significant cont ribution of electronic or polar properties was found to a describe the toxicity within this set of compounds.