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.
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.
Clark
R D
RD
Institute of Organic Chemistry, Syntex Research, Palo Alto, California 94304.
Berger
J
J
Garg
P
P
Weinhardt
K K
KK
Spedding
M
M
Kilpatrick
A T
AT
Brown
C M
CM
MacKinnon
A C
AC
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002540:Cerebral Cortex; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004146:Dioxanes / Q000378:metabolism; D019329:Idazoxan; D007093:Imidazoles / Q000138:chemical synthesis / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis / Q000378:metabolism*; D007546:Isoquinolines / Q000138:chemical synthesis / Q000378:metabolism*; D008024:Ligands; D011224:Prazosin / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015016:Yohimbine / Q000378:metabolism
D004146:Dioxanes; D007093:Imidazoles; D007211:Indoles; D007546:Isoquinolines; D008024:Ligands; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D011224:Prazosin; D019329:Idazoxan