| Abstract
| - A series of N-(iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines was synthesized and assayedin vitro for their dopaminergic and α-adrenergic activity. Structure−activity relationship (SAR)analysis revealed that the tested benzoquinolines exhibited activity at the D1 rather than theD2 receptor sites in contrast to the D2 receptor subfamily activity reported for theiraminotetralin congeners. N-Iodopropenyl substitution was apparently a decisive factor for D1activity independent of ring substitution pattern. Considering the structural factors influencingα-adrenergic activity, in a general trend, N-iodopropenyl analogues were α1-active, with thering-hydroxylated congeners exhibiting the highest affinity. Affinity to the α2 receptor waseven higher with no detectable trend of SAR. However, a combination of the linear arrangementof the [g]-ring system, combined with the ring hydroxyl and the N-iodopropenyl substitutionin compound 5c, resulted in a significant enhancement of α2 activity in this series asdemonstrated by an IC50 value of 0.5 nM. A new synthetic approach to the [g]benzoquinolinesystem is also described.
|
