Abstract
Novel imidazole frameworks have been identified as potent partial agonists of the alpha(1A) adrenergic receptor, with good selectivity over the alpha(1B), alpha(1D) and alpha(2A) receptor sub-types. Nitrile 28 possessed attractive CNS drug-like properties with good membrane permeability and no P-pg mediated efflux. 28 also possessed excellent solubility, metabolic stability and wide ligand selectivity.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Adrenergic alpha-1 Receptor Agonists*
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Adrenergic alpha-2 Receptor Agonists
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Animals
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Cell Line
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Dogs
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry*
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Imidazoles / pharmacokinetics
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Receptors, Adrenergic, alpha-1 / metabolism
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Receptors, Adrenergic, alpha-2 / metabolism
Substances
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ADRA1A protein, human
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ADRA1B protein, human
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ADRA1D protein, human
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ADRA2A protein, human
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Adrenergic alpha-1 Receptor Agonists
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Adrenergic alpha-2 Receptor Agonists
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Imidazoles
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Receptors, Adrenergic, alpha-1
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Receptors, Adrenergic, alpha-2