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N ‐(1‐Cyanoalkyl)‐ N ‐hydroxyureas
Author(s) -
Camehn Rainer,
Rehse Klaus
Publication year - 2000
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/(sici)1521-4184(200001)333:1<27::aid-ardp27>3.0.co;2-z
Subject(s) - chemistry , antithrombotic , nitric oxide , in vivo , in vitro , porphyrin , thrombus , stereochemistry , medicinal chemistry , biochemistry , organic chemistry , surgery , medicine , microbiology and biotechnology , biology
Nineteen N ‐(1‐cyanoalkyl)‐ N ‐hydroxyureas comprising aliphatic ( 3a‐i, 4a, b, and 5a ) and aromatic ( 3j‐n, 4c, 5b ) compounds were prepared, fourteen of them for the first time, and tested for antithrombotic (p.o. administration to rats, 60 mg/kg) effects. The N ‐(1‐cyanocyclohexyl)‐ N ‐hydroxy‐N′‐phenylurea ( 3j ) was most potent and inhibited laser‐induced (35 mW, 50 ms) thrombus formation in arterioles by 21% and that in venules by 15%. The compounds form nitric oxide in vitro by the addition of a Fe 3+ ‐porphyrin complex and an oxygen donor. Moreover, the most active compound 3j in vivo exhibits the highest NO formation in vitro . Furthermore, it was shown that the cyano group is essential for the desired activities and NO formation. These results suggest that the title compounds act as NO donors.