[Hypertensive action of 5-(beta-aminoethyl)aminoisoxazoles: synthesis and screening of isoxazolopyrazines and isoxazolodiazepines].
The 5-aminoisoxazole 1 is converted via the 4-nitro derivative to the 4,5-diamino compound 4, which cyclises with glyoxal to yield the isoxazolo[4,5-b)pyrazine 5. Decomposition of the isoxazole moiety is always observed in experiments to hydrogenate partially the pyrazine ring and to phenylate the N-atom, respectively. Therefore, the corresponding tetrahydro derivative 6 is prepared from 4 and 1,2-ethandiol ditosylate. Starting with benzohydroxamic acid chloride and a cyanoacetic acid amide the tetrahydro isoxazolo[5,4-e]1,4-diazepinone-4 18 is synthesized. All new compounds are characterized by their spectroscopic data, the reaction mechanisms are discussed. Using the model of the pithed and the anaesthetized rat, resp., the pyrazino- and diazepino-isoxazoles (compounds 5, 6, 13, 18) have less or no hypertensive activity as compared to the corresponding derivatives with fully flexible side chains.
Dannhardt
G
G
Institut für Pharmazeutische Chemie, Johann Wolfgang Goethe-Universität, Frankfurt am Main.
Dominiak
P
P
Laufer
S
S
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D006339:Heart Rate / Q000187:drug effects; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D001381:Azepines; D007555:Isoxazoles; D011719:Pyrazines
Hypertensiv wirksame 5-(beta-Aminoethyl)aminoisoxazole: Synthese und Prüfung von Isoxazolopyrazinen und Isoxazolodiazepinen.