Application of the Free-Wilson technique to structurally related series of homologs. Quantitative structure-activity relationship studies of narcotic analgetics

Abstract
A series of benzomorphans [91] with ED50 values determined in vivo by the hot-plate method in mice was analyzed by the modified Free-Wilson method. The QSAR [quantitative structure-activity relationships] yielded 36 substituent constants (ai) with contributions to the overall activity in agreement with experimental data. Substituent constant values obtained for benzomorphans were used in calculating log (1/C) [c = mol/kg of test animal] values for 6 morphinans. An excellent correlation was obtained (r = 0.95) between the 6 calculated and observed activities. The possibility of extending the Free-Wilson approach from 1 series of homologues to another was demonstrated.

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