Structure-activity relationships in 1,4-benzodioxan-related compounds. 5. Effects of modification of the side chain on alpha-adrenoreceptor blocking activity.
The observation that the insertion of a phenyl ring at position 3 of WB 4101 (1) afforded a potent and selective alpha 1-adrenoreceptor antagonist, phendioxan (2), prompted us to investigate the effect on alpha-adrenoreceptor blocking activity of replacing a hydrogen atom at the 2-position or on the 2-ylmethyl moiety of 1 and 2 by a methyl, ethyl or phenyl group. Thus compounds 3-11 were synthesized and their blocking activity and relative selectivity on alpha 1- and alpha 2-adrenoreceptors were evaluated in the isolated rat vas deferens in comparison to 1 and 2. The results of such investigation showed that this structural modification caused a decrease in affinity for alpha-adrenoreceptors.
Quaglia
W
W
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
Giannella
M
M
Marucci
G
G
Piergentili
A
A
Pigini
M
M
Tayebati
S K
SK
Melchiorre
C
C
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane