• Medientyp: E-Artikel
  • Titel: New NO‐Donors with Antithrombotic and Vasodilating Activities, Part 17. Arylazoamidoximes and 3‐Arylazo‐1,2,4‐oxadiazol‐5‐ones
  • Beteiligte: Rehse, Klaus; Bade, Stephan; Harsdorf, Angela; Clement, Bernd
  • Erschienen: Wiley, 1997
  • Erschienen in: Archiv der Pharmazie
  • Sprache: Englisch
  • DOI: 10.1002/ardp.19973301207
  • ISSN: 0365-6233; 1521-4184
  • Schlagwörter: Drug Discovery ; Pharmaceutical Science
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Seven arylazoamidoximes (<jats:bold>3</jats:bold>), six phenoxycarbonyl derivatives (<jats:bold>4</jats:bold>), and six 1,2,4‐oxadiazol‐5‐ones (<jats:bold>5</jats:bold>) have been prepared and their structure and purity established by spectroscopy and elemental analysis. In the EI mass spectra ready elimination of NO from the title amidoximes was observed. A new addition reaction of <jats:bold>3a</jats:bold> with hydrochloric acid to 4‐chlorophenylhydroazoamidoxime <jats:bold>7</jats:bold> is described. The compounds were tested for nitric oxide dependent biological properties, i.e. platelet aggregation, antithrombotic effects, and decrease in blood pressure. In arterioles of rats 5/19 compounds inhibited the formation of thrombi with a laser beam by ≥ 20% 2 h after oral administration of 60 mg/kg. Among these are three amidoximes (<jats:bold>3a, 3e, 3f</jats:bold>), one phenoxycarbonyl derivative (<jats:bold>4a</jats:bold>), and one oxadiazolone (<jats:bold>5a</jats:bold>). With the 4‐chlorophenylazoamidoxime <jats:bold>3c</jats:bold> a long lasting (24 h) decrease of blood pressure in spontaneously hypertensive rats was observed. Microsomal fractions of rat liver oxidize arylazoamidoximes and generate nitric oxide (e.g. <jats:bold>3a</jats:bold> and <jats:bold>3b</jats:bold>). NO was measured by the oxyhemoglobin assay. The influence of SOD, pretreatment of the rats with dexamethasone, as well as kinetic parameters were determined. Type <jats:bold>3</jats:bold> compounds, therefore, are a new class of NO donors. Type <jats:bold>4</jats:bold> and <jats:bold>5</jats:bold> compounds function as their prodrugs.</jats:p>