New NO donors with antithrombotic and vasodilating activities, part 25. Hydroxylamine derivatives.
Twelve ethoxycarbonyl or phenylsulfonyl derivatives as prodrugs of hydroxylamine or phenylhydroxylamine were prepared and tested for antiplatelet (in vitro, Born test) antithrombotic (in vivo thrombosis model), and antihypertensive (in vivo, SHR rats) effects. In the Born test N,N-bisphenylsulfonylhydroxylamine (10) was most active (IC50 = 11 mumol/L). The N-ethoxycarbonyl-phenylhydroxylamine (7) was the most potent antithrombotic compound. It inhibited the thrombus formation in mesenteric arterioles of rats by 39% after a single p.o. dose of 60 mg/kg. Compound 7 lacked any antihypertensive activity. It, therefore, had been possible to separate completely the antithrombotic activities from antihypertensive properties in suitable hydroxylamine derivatives.
Rehse
K
K
Institut für Pharmazie I, Freie Universität Berlin, Germany.
Shahrouri
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006898:Hydroxylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D005343:Fibrinolytic Agents; D006898:Hydroxylamines; D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs