DOPAMINERGIC AND SEROTONERGIC ACTIVITIES OF IMIDAZOQUINOLINONES AND RELATED-COMPOUNDS

The synthesis of 5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (5 ), a potent dopamine D2 agonist showing high dopamine/serotonin (5HT1A ) selectivity, is described. Dopaminergic activity is associated with the (R)-enantiomer of 5; the (S)-enantiomer shows no dopaminergic acti vity. A series of analogues where the imidazolone ring was modified to various 5- or 6-membered heterocyclic rings were prepared. Some of th ese compounds showed a combination of dopaminergic and serotonergic ac tivity, while one compound, -tetrahydro-3H,5H-pyrido[3,2,1-ij]quinazol in-3-one (24), was a selective serotonergic agonist. Various analogues of 5 where the dipropylamine substituent was modified were prepared. Most of these showed reduced dopaminergic activity, while several were as potent as 5 at the serotonin 5HT1A receptor. Orientations for the new compounds at dopamine and serotonin receptors are proposed and com pared with those of other tricyclic ligands known to have high affinit y at these receptors.