Studies on antiplatelet agents from natural safrole. II. Synthesis and pharmacological properties of novel functionalized oxime O-benzylether derivatives.
In an ongoing research program aiming at the synthesis and pharmacological evaluation of new possible prototype candidates exploring the molecular hybridation and bioisosterism principles for molecular designing, we describe in this paper the design and synthesis of a series of new functionalized oxime O-benzylethers (4a-b) and (14a-b) as antiplatelet agents based on the inhibition of arachidonic acid (AA) cascade enzymes. For the synthesis of these new bioactive derivatives we used safrole (5), a Brazilian abundant natural product, as starting material. The platelet anti-aggregating evaluation of these oxime O-benzylether compounds (4a-b) and (14a-b) in model induced by ADP, collagen and AA, has permitted to evidence an antithrombotic profile to these new derivatives, being the most active the derivative methyl [[3,4-methylenedioxyphenyl]methylene]amino]oxy]-4-methylenephenylacet ic acid (14a).
Reis
A L
AL
Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Brazil.
Ormelli
C B
CB
Miranda
A L
AL
Fraga
C A
CA
Barreiro
E J
EJ
D000818:Animals; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D012451:Safrole / Q000138:chemical synthesis* / Q000494:pharmacology
D010091:Oximes; D010975:Platelet Aggregation Inhibitors; D012451:Safrole