Octopaminergic agonists for the cockroach neuronal octopamine receptor

The compounds 1-(2,6-diethylphenyl)imidazolidine-2-thione and 2-(2,6-diethylphenyl)imidazolidine showed the almost same activity as octopamine in stimulating adenylate cyclase of cockroach thoracic nervous system among 70 octopamine agonists, suggesting that only these compounds are full octopamine agonists and other compounds are partial octopamine agonists. The quantitative structure-activity relationship of a set of 22 octopamine agonists against receptor 2 in cockroach nervous tissue, was analyzed using receptor surface modeling. Three-dimensional energetics descriptors were calculated from receptor surface model/ligand interaction and these three-dimensional descriptors were used in quantitative structure-activity relationship analysis. A receptor surface model was generated using some subset of the most active structures and the results provided useful information in the characterization and differentiation of octopaminergic receptor. Abbreviation: / AEA: arylethanolamine AII: 2-(arylimino)imidazolidine AIO: 2-(arylimino)oxazolidine AIT: 2-(arylimino)thiazolidine APAT: 2-(α-phenylethylamino)-2-thiazoline BPAT: 2-(β-phenylethylamino)-2-thiazoline CAO: 2-(3-chlorobenzylamino)-2-oxazoline DCAO: 2-(3,5-dichlorobenzylamino)-2-oxazoline DET5: 2-(2,6-diethylphenylimino)-5-methylthiazolidine DET6: 2-(2,6-diethylphenylimino)thiazine EGTA: ethylene glycol bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid GFA: genetic function approximation G/PLS: genetic partial least squares IND: 2-aminomethyl-2-indanol LAH: lithium aluminum hydride MCSG: maximum common subgroup MCT6: 2-(2-methyl-4-chlorophenylimino)thiazine OA: octopamine PLS: partial least squares QSAR: quantitative structure-activity relationship SBAT: 2-(substituted benzylamino)-2-thiazoline SD: the sum of squared deviations of the dependent variable values from their mean SPIT: 3-(substituted phenyl)imidazolidine-2-thione THI: 2-amino-1-(2-thiazoyl)ethanol TMS: tetramethyl silane