Modelling of adrenoceptor ligand targets based on novel medium- or macro-sized fused nitrogen heterocyclic systems.

Novel medium- and macro-sized heterocyclic compounds were assessed for their potential as subtype-selective adrenergic ligands. Their conformational flexibilities were investigated and their geometric shapes were compared to rigid lead compounds of known selectivity. In the case of alpha 1A selective antagonists, interesting potential targets for synthesis and evaluation were identified by 'opening up' various rings of the fused-ring lead compound 1 by shared-bond cleavage. For alpha 2 selective ligands, compound 6 was the lead compound and the possibility of mimicking the fused-ring system via intramolecular hydrogen bonding was investigated. None of the potential targets were closely enough related in this case to the lead compound to warrant synthesis.