ABSTRACT
Starting from 14C-benzene (--)-erythro-norephedrine (14C-1-norephedrine) was obtained in a 6-step synthesis. 14C-1-Norephedrine functioned as an intermediate for the synthesis of the carbon labelled partial beta-agonist oxyfedrine hydrochloride (ildamen) and the new positive inotropic agent D 13 625 (alifedrine hydrochloride).
Subject(s)
Oxyfedrine/chemical synthesis , Phenylpropanolamine/chemical synthesis , Propiophenones/chemical synthesis , Carbon Radioisotopes , Chemical Phenomena , Chemistry , Isotope Labeling , Oxyfedrine/analogs & derivativesABSTRACT
The synthesis of [R-(R*,S*)]-7-[2-[(2-hydroxy-1-methyl-2-phenylethyl)amino]-ethyl]-3,7-dihydro-1 ,2-dimethyl-1H-purine-2,6-dione (Cafedrine) and its stereoisomers is reported. By means of 1H- and 13C-nmr spectroscopy the relative configuration of the two asymmetric centres is ascertained and the absolute configuration is discussed. The EI-mass spectrometric fragmentation of cafedrine has been elucidated.
Subject(s)
Blood Circulation/drug effects , Phenylpropanolamine/analogs & derivatives , Theophylline/analogs & derivatives , Chemical Phenomena , Chemistry , Gas Chromatography-Mass Spectrometry , Magnetic Resonance Spectroscopy , Molecular Conformation , Phenylpropanolamine/analysis , Phenylpropanolamine/chemical synthesis , Stereoisomerism , Theophylline/analysis , Theophylline/chemical synthesisABSTRACT
Biotransformation of 7-(3-[2-(3,5-dihydroxyphenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, Bronchospasmin), a beta 2-adrenergic drug recently introduced into therapeutic use, leads to the same main metabolite in animals and in man. By mass-spectroscopy and by synthesis its structure was shown to be tetrahydroisoquinoline derivative which is produced from reproterol by uptake of an additional carbon atom concomitant with cyclization.
Subject(s)
Adrenergic beta-Agonists/metabolism , Metaproterenol/analogs & derivatives , Theophylline/analogs & derivatives , Adrenergic beta-Agonists/chemical synthesis , Animals , Bile/metabolism , Biotransformation , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Electrophoresis , Mass Spectrometry , Metaproterenol/chemical synthesis , Metaproterenol/metabolism , Rats , Theophylline/chemical synthesis , Theophylline/metabolismABSTRACT
Structure-activity relationships of 90 bronchospasmolytic compenylethyl-aminoalkyl-xanthines are reported. Particularly the influence of substituents in the phenyl moiety as well as of the carbon bridge between the xanthine residue and the beta-phenylethylamine moiety is described. 2. A method is shown for the selection of one optimally bronchospasmolytic substance from many potential compounds synthetised via multiple screening steps to profound biological studies.
Subject(s)
Bronchodilator Agents , Phenethylamines/pharmacology , Xanthines/pharmacology , Animals , Bronchi/drug effects , Chemical Phenomena , Chemistry , Dogs , Female , Guinea Pigs , Heart Rate/drug effects , Isoproterenol/pharmacology , Male , Structure-Activity RelationshipABSTRACT
Synthesis of radioactively labelled 7-(3-[2-(3,5-dihydroxy-phenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol) as needed for pharmacokinetic examinations, is described. The 14C-malonic diethyl ester was proven to be the suitable starting compound. The synthesis of the tritium-labelled reproterol is briefly described.
Subject(s)
Phenethylamines/chemical synthesis , Xanthines/chemical synthesis , Bronchodilator Agents/chemical synthesis , Carbon Radioisotopes , Chemical Phenomena , Chemistry , Isotope Labeling , TritiumABSTRACT
New theophylline and theobromine derivatives are synthetized from the beta-phenylethylaminoalkyl-xanthines, whose phenyl substituent is substitutent by one or two hydroxyl groups and partially also by other substituents. Different methods of synthesis are described, among them the production of the bronchospasmolytic 7-(3-[2-(3,5-dihydroxyphenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol-HCl).
