Abstract
A series of derivatives structurally related to biphenyline (3) was designed with the aim to modulate selectivity toward the alpha(2)-AR subtypes. The results obtained demonstrated that the presence of a correctly oriented function with positive electronic effect (+sigma) in portion X of the ligands is an important factor for significant alpha(2C)-subtype selectivity (imidazolines 5, 13, 16, and 19). Homology modeling and docking studies support experimental data and highlight the crucial role for the hydrogen bond between the pyridine nitrogen in position 3 of 5 and the NH-indole ring of Trp6.48, which is favorably oriented in the alpha(2C)-subtype, only.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic alpha-2 Receptor Agonists*
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Amino Acid Sequence
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Animals
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Biphenyl Compounds / chemical synthesis*
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Biphenyl Compounds / chemistry
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Biphenyl Compounds / pharmacology
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CHO Cells
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Cricetinae
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Cricetulus
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry
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Imidazoles / pharmacology
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Models, Molecular
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Molecular Sequence Data
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Oxazoles / chemical synthesis
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Oxazoles / chemistry
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Oxazoles / pharmacology
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Radioligand Assay
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Receptors, Adrenergic, alpha-2 / chemistry
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Sequence Homology, Amino Acid
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Stereoisomerism
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Structure-Activity Relationship
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Thiazoles / chemical synthesis
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Thiazoles / chemistry
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Thiazoles / pharmacology
Substances
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ADRA2C protein, human
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Adrenergic alpha-2 Receptor Agonists
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Biphenyl Compounds
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Imidazoles
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Oxazoles
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Receptors, Adrenergic, alpha-2
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Thiazoles