6,7-Dihydro-5H-pyrrolo[1,2-a] imidazoles as potent and selective alpha1A adrenoceptor partial agonists.
Novel pyrroloimidazoles 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 subtypes. Pyrimidine 19 possessed attractive CNS drug-like properties with good membrane permeability and no evidence for P-gp mediated efflux.
Roberts
Lee R
LR
Department of Chemistry, Pfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK. lee.roberts@pfizer.com
Fish
Paul V
PV
Ian Storer
R
R
Whitlock
Gavin A
GA
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 / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; 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; D011743:Pyrimidines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2