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

Gavin A Whitlock; Paul E Brennan; Lee R Roberts; Alan Stobie

doi:10.1016/j.bmcl.2009.03.162

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

Bioorg Med Chem Lett. 2009 Jun 1;19(11):3118-21. doi: 10.1016/j.bmcl.2009.03.162. Epub 2009 Apr 7.

Authors

Gavin A Whitlock¹, Paul E Brennan, Lee R Roberts, Alan Stobie

Affiliation

¹ Pfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK. gavin.whitlock@pfizer.com

PMID: 19394220
DOI: 10.1016/j.bmcl.2009.03.162

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

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 / chemical synthesis
Imidazoles / chemistry*
Imidazoles / pharmacokinetics
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
Receptors, Adrenergic, alpha-1
Receptors, Adrenergic, alpha-2