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 mediated efflux. 28 also possessed excellent solubility, metabolic stability and wide ligand selectivity.
Whitlock
Gavin A
GA
Pfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK. gavin.whitlock@pfizer.com
Brennan
Paul E
PE
Roberts
Lee R
LR
Stobie
Alan
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D002460:Cell Line; D004285:Dogs; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism
C547713:ADRA1A protein, human; C547716:ADRA1B protein, human; C547719:ADRA1D protein, human; C547768:ADRA2A protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D007093:Imidazoles; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2