Synthesis and pharmacological evaluation of imidazoline sites I1 and I2 selective ligands.
Journal - Bioorganic & medicinal chemistry (England )
Several series of 2-aryl or heterocyclic-imidazoline compounds have been prepared and evaluated in vitro as imidazoline sites (I1 and I2) and alpha-adrenergic (alpha1 and alpha2) receptor ligands. Their pKi values indicate that linkage of the imidazoline moiety at the 2-position with an aromatic substituent dramatically decreases alpha-adrenergic affinity. I1 sites are more accessible by phenyl imidazolines substituted by a methyl or a methoxy group at the ortho or meta position. Indeed, 2-(2'-methoxyphenyl)-imidazoline (17) is one of the best I1 ligands ever reported (pKi = 8.53 and I1/I2 > 3388). On the other hand, I2 selectivity increases in the presence of a methyl group in the para position. The original compound, 2-(3'-fluoro-4'-tolyl)-imidazoline (31) is a new potent ligand for the I2 sites with high selectivity (pKi = 8.53 and I2/I1 > 3388).
|ISSN : ||0968-0896|
|Mesh Heading : ||Adrenal Glands Animals Antihypertensive Agents Binding Sites Cattle Cell Membrane Cerebral Cortex Imidazoles Imidazoline Receptors Kidney Cortex Ligands Rabbits Radioligand Assay Receptors, Adrenergic, alpha-1 Receptors, Adrenergic, alpha-2 Receptors, Drug Structure-Activity Relationship ultrastructure chemical synthesis metabolism chemistry metabolism ultrastructure ultrastructure metabolism metabolism|
|Mesh Heading Relevant : ||chemical synthesis pharmacology metabolism|