Synthesis, biological data and correlation analysis in a set of analgesic drugs

A set of ortho-disubstituted benzene derivatives (2-X--C6H4NH--Y) designed as analgesics has been studied. Some physicochemical properties which are potentially correlated with the considered pharmacological activities are determined. Quantitative structure-activity relationships (QSAR) show that the analgesic potency (writhing test) is a function of the hydrophobic-lipophilic parameters associated with the structures under study. Since the derivatives are inactive or very poor inhibitors of prostaglandin biosynthesis, the appropriate modulation of substituents may maximize the differentiation between anti-nociceptive and analgesic activity.