Dopaminergic and serotonergic activities of imidazoquinolinones and related compounds.

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Moon MW, Morris JK, Heier RF, Chidester CG, Hoffmann WE, Piercey MF, Althaus JS, Von Voigtlander PF, Evans DL, Figur LM, et al.

Dopaminergic and serotonergic activities of imidazoquinolinones and related compounds.

J Med Chem. 1992 Mar 20;35(6):1076-92.

PubMed ID

1348089 [ View in PubMed

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Abstract

The synthesis of 5-(dipropylamino)-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 activity. A series of analogues where the imidazolone ring was modified to various 5- or 6-membered heterocyclic rings were prepared. Some of these compounds showed a combination of dopaminergic and serotonergic activity, while one compound, 6-(dipropylamino)-1,2,6,7-tetrahydro-3H,5H-pyrido[3,2,1- ij]quinazolin-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 compared with those of other tricyclic ligands known to have high affinity at these receptors.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Apomorphine	5-hydroxytryptamine receptor 1A	Ki (nM)	534	N/A	N/A	Details
Buspirone	5-hydroxytryptamine receptor 1A	Ki (nM)	6.6	N/A	N/A	Details