Synthesis, characterization and interaction mechanism of new oxadiazolo-phthalimides as peripheral analgesics.: IV

The synthesis, characterization and spectroscopic studies of compounds 6a-g with analgesic activity is described. A new model of interaction between the drug and the enzyme is suggested. Application of the Resonance Valence Bond theory led us to propose. for the first time, an entirely new mechanism involving an electron transfer from the amino acid residue of the enzyme to the drug. Theoretical studies of various transition states involved in the interaction mechanism employing the semi-empirical molecular orbital calculations (AMI method) have been carried out. This article also deals with an extensive study of the structure-activity relationships of seven oxadiazolo-phthalimides 6a-g. (C) 2003 Elsevier B.V. All rights reserved.