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New NO‐Donors with Antithrombotic and Vasodilating Activities, Part 13: Pyrazol‐4‐one 1,2‐Dioxides and 4‐Hydroxyiminopyrazole 1,2‐Dioxides
Author(s) -
Rehse Klaus,
Müller Ulrich
Publication year - 1995
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19953281107
Subject(s) - antithrombotic , chemistry , thrombus , in vivo , stereochemistry , pyrazolone , vasodilation , platelet , platelet aggregation , pharmacology , medicinal chemistry , medicine , microbiology and biotechnology , biology
Twenty pyrazol‐4‐one 1,2‐dioxides and eleven 4‐hydroxyiminopyrazole 1,2‐dioxides were prepared and tested for their antiplatelet activity (Born test with collagen). Six compounds which all belong to the pyrazolone series inhibited the platelet aggregation half‐maximally in submicromolar concentrations (200–800 nmol/L). In positions 3 and 5, these compounds bear at least one ( 15, 16, 24, 31 ) or two substituents ( 7, 29 ) with electron‐withdrawing groups. Among them are aromatic moieties like 4‐hydroxysulfonylphenyl ( 7 ), 4‐cyanophenyl ( 16 ), 4‐chlorophenyl ( 15 ), phenyl ( 24 ) or carboxylic acid esters ( 29 ). Two compounds were investigated in an in vivo thrombosis model ( 1, 31 ). 2h after oral administration of 60 mg/kg 1 to rats in arterioles 69 % inhibition of thrombus formation (venules 40 %) was observed.