Synthesis of the new alpha- and beta-adrenergic antagonist 1-[1-(2-benzodioxanylmethyl)-4-piperidyl]amino-3-(1-naphthoxy)-2- propanol.
The synthesis and in vitro alpha- and beta-adrenergic blocking potency of 1-[1-(2-benzodiaxanylmethyl)-4-piperidyl]amino-3-(1-naphthoxy-2-pr opanol (I) are described. Thus, N-benzyl-4piperidone was protected and debenzylated to the carbamate (V), which upon alkaline hydrolysis and acylation gave benzodioxanic amide (IX). Reduction of the amide group, deprotection of the ketone function of (X), and reductive amination gave the 4-aminopiperidine (XIII), which was finally condensed with the appropriate epoxide to yield the aminopropanol (I). Compound (I) is formally derived from a combination of piperoxan (II) and propranolol (III), and was approximately 10 times less potent than each one of these drugs, as an alpha- and beta-adrenergic blocker respectively.
Mauleón
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D
Departamento de Farmacología y Química Terapéutica, Facultad de Farmacia, Universidad de Barcelona, Spain.
Antúnez
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S
Rosell
G
G
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis*; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010883:Piperoxan / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D011433:Propranolol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D051381:Rats; D014132:Trachea / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; C065761:1-(1-(2-benzodioxanylmethyl)-4-piperidiyl)amino-3-(1-naphthoxy)-2-propanol; D011433:Propranolol; D010883:Piperoxan