Potent and selective alpha1A adrenoceptor partial agonists--novel imidazole frameworks

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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-06, Vol.19 (11), p.3118-3121
Main Authors: Whitlock, Gavin A, Brennan, Paul E, Roberts, Lee R, Stobie, Alan
Format: Article
Language:English
Subjects:
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-2 Receptor Agonists
Animals
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Cell Line
Dogs
Humans
Imidazoles - chemical synthesis
Imidazoles - chemistry
Imidazoles - pharmacokinetics
Receptors, Adrenergic, alpha-1 - metabolism
Receptors, Adrenergic, alpha-2 - metabolism
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Summary: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.
ISSN:1464-3405
DOI:10.1016/j.bmcl.2009.03.162