| Title | Affinity of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines for alpha-adrenoceptors. Differential affinity of imidazolines for the [3H]idazoxan-labeled alpha 2-adrenoceptor vs the [3H]yohimbine-labeled site. |
| Publication Type | Journal Article |
| Year of Publication | 1990 |
| Authors | Clark RD, Berger J, Garg P, Weinhardt KK, Spedding M, Kilpatrick AT, Brown CM, Mackinnon AC |
| Journal | Journal of medicinal chemistry |
| Volume | 33 |
| Issue | 2 |
| Pagination | 596-600 |
| Date Published | 1990 Feb |
| ISSN | 0022-2623 |
| Keywords | Animals, Binding Sites, Binding, Competitive, Cerebral Cortex, Chemistry, Physical, Dioxanes, Idazoxan, Imidazoles, Indoles, Isoquinolines, Ligands, Physicochemical Phenomena, Prazosin, Radioligand Assay, Rats, Receptors, Adrenergic, alpha, Structure-Activity Relationship, Yohimbine |
| Abstract | A series of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines were prepared and tested for alpha 1- and alpha 2-adrenoceptor affinity with radioligand binding. Several compounds, 5-fluoro-(5h), 5-chloro-(5j), 5,8-dimethoxy- (5r), and 5,8-dimethoxy- (5r),1-methyl- (5s) 2-(tetrahydroisoquinolin-2- ylmethyl)imidazoline, were found to be selective alpha 2-adrenoceptor ligands on the basis of displacement of [3H]yohimbine from rat cerebral cortical membranes. One compound, 2-[(8-chloro tetrahydroisoquinolin-2-yl)methyl]imidazoline (5m), showed a 36-fold difference in affinity for the [3H]idazoxan-labeled alpha 2-adrenoceptor relative to the [3H]yohimbine-labeled site, which may be evidence for alpha 2-adrenoceptor subtypes. |
| Alternate Journal | J. Med. Chem. |
