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

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Abstract

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 α1A 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 α2 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.

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Authors and Affiliations

  1. Department of Chemistry, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia

    Renate Griffith & John B. Bremner

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  1. Renate Griffith
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  2. John B. Bremner
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Griffith, R., Bremner, J.B. Modelling of adrenoceptor ligand targets based on novel medium- or macro-sized fused nitrogen heterocyclic systems. J Comput Aided Mol Des 13, 69–78 (1999). https://doi.org/10.1023/A:1008087131806

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