title: [Synthesis of the highly cardioselective beta-sympatholytic pacrinolol].
abstract: The synthesis is described of the enantiomerically pure (-)-3-(3,4-dimethoxyphenylethylamino)-2-hydroxypropoxy] phenyl]-cis-crotonic acid nitrile (13b) (free base) and its hydrochloride (13c) (pacrinolol, Hoe 224 A) starting from p-hydroxyacetophenone (1) and racemic epichlorohydrin (2). The p-(2,3-oxidopropoxy)acetophenone (2) resulting from this reaction is C-homologisized to (8); reactions of this with homoveratrylamine (9) leads to (10a), the racemic structural analog of (13b). Resolution of the racemate is achieved by fractional crystallisation of the diastereoisomeric mandelates (13a) and (14a) to afford the enantiomerically pure title compound (13c) and its dextrarotatory optical antipode (14c). Structural confirmation of (13b) and (13c) was achieved through physicochemical and spectroscopic data especially from the 1H-NMR- and MS-spectra. Pacrinolol (13c) is a highly cardioselective beta-sympathicolytic with significant and long acting blood pressure lowering properties (intravenous and oral in the dog).
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D002627:Chemistry, Physical; D004285:Dogs; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011412:Propanolamines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C041429:pacrinolol
vernacular_title: Synthese des hochgradig kardioselektiv wirksamen beta-Sympathikolytikums Pacrinolol.