STRUCTURE AND OCTOPAMINERGIC-AGONIST ACTIVITY OF 2-(ARYLIMINO)OXAZOLIDINES AND 2-(SUBSTITUTED BENZYLAMINO)-2-OXAZOLINES

The quantitative structure-activity relationship of 2-(arylimino)oxazo lidines (AIOs) and 2-(substituted benzylamino)-2-oxazolines (SBOs) in stimulating adenylate cyclase prepared from thoracic nerve cords of th e American cockroach Periplaneta americana L. was examined using param eters calculated by a molecular orbital procedure. The more hydrophobi c and the smaller the highest occupied molecular orbital (HOMO) and mo lecular connection (MC) values, the greater the V-max values. The larg er similarity comparison (SC) values (the more similar structure to OA the compound has), the greater the V-max values. The larger the molar refractivity (MR) and V-max values, the greater the activity in term of K-a. 2-Alkyl, 4-halogen substitution in the phenyl ring of AIOs gav e the greatest enzyme activation. Compounds incorporating a halogen(s) in the phenyl ring of SBO compounds favor octopaminergic-agonist acti vity. Superimposition of energy minimized octopamine (OA) and 2-(2,3,4 -trichlorophenylimino) oxazolidine (21) revealed structural and confor mational similarities that might account for the high activity of 21 c ompared to the corresponding thiazolidine derivative, which is not sup erimposed well with OA. (C) 1997 Academic Press.