6,7-Dihydro-5H-pyrrolo[1,2-a] imidazoles as potent and selective alpha1A adrenoceptor partial agonists

Lee R Roberts; Paul V Fish; R Ian Storer; Gavin A Whitlock

doi:10.1016/j.bmcl.2009.03.166

6,7-Dihydro-5H-pyrrolo[1,2-a] imidazoles as potent and selective alpha1A adrenoceptor partial agonists

Bioorg Med Chem Lett. 2009 Jun 1;19(11):3113-7. doi: 10.1016/j.bmcl.2009.03.166. Epub 2009 Apr 18.

Authors

Lee R Roberts¹, Paul V Fish, R Ian Storer, Gavin A Whitlock

Affiliation

¹ Department of Chemistry, Pfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK. lee.roberts@pfizer.com

PMID: 19414260
DOI: 10.1016/j.bmcl.2009.03.166

Abstract

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.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Adrenergic alpha-1 Receptor Agonists*
Adrenergic alpha-2 Receptor Agonists
Animals
Cell Line
Dogs
Humans
Imidazoles / chemistry*
Imidazoles / metabolism
Imidazoles / pharmacology*
Microsomes, Liver / metabolism
Pyrimidines / chemistry*
Pyrimidines / metabolism
Pyrimidines / pharmacology*
Receptors, Adrenergic, alpha-1 / metabolism
Receptors, Adrenergic, alpha-2 / metabolism

Substances

ADRA1A protein, human
ADRA1B protein, human
ADRA1D protein, human
ADRA2A protein, human
ATP Binding Cassette Transporter, Subfamily B, Member 1
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-2 Receptor Agonists
Imidazoles
Pyrimidines
Receptors, Adrenergic, alpha-1
Receptors, Adrenergic, alpha-2