Derivatives of beta-adrenergic antagonists. N-Nitrosopropranolol and N-hydroxypropranolol and its aldonitrone.
Potential precursors to chemically reactive species derived from the beta-adrenergic antagonist propranolol were synthesized and tested for mutagenicity in the Ames Salmonella assay. N-Hydroxypropranolol (1), the corresponding aldonitrone, 3-(1-naphthoxy)-2-hydroxypropionaldehyde N-isopropylnitrone (2), and N-nitrosopropranolol (3) were prepared and tested. N-Hydroxypropranolol (1) was obtained by direct alkylation of 3-(1-naphthoxy)-1-bromo-2-propanol with N-isopropylhydroxylamine and isolated as its neutral oxalate or HBr salt. The aldonitrone (2) was obtained by mercuric oxide oxidation of the hydroxylamine. N-Nitrosopropranolol (3) was prepared by treating propranolol with nitrous acid. None of the compounds was mutagenic in the Ames assay with Salmonella typhimurium TA-98 and TA-100 strains, either in the absence or in the presence of the S-9 liver fraction from Arochlor 1254 treated rats. None of the compounds was significantly toxic to the bacteria, except for slight toxicity of the oxalate salt of 1.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D008099:Liver / Q000187:drug effects; D008297:Male; D009152:Mutagenicity Tests; D009602:Nitrosamines / Q000494:pharmacology*; D011433:Propranolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D009602:Nitrosamines; C037602:N-hydroxypropranolol; C037603:propranolol N-aldonitrone; C037601:N-nitrosopropranolol; D011433:Propranolol