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Synthesis of pyrazole derivatives as potential bioisosteres of thromboxane‐synthetase inhibitors
Author(s) -
Barreiro Eliezer J.,
Freitas Antonio C. C.
Publication year - 1992
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570290220
Subject(s) - chemistry , pyrazole , yield (engineering) , platelet aggregation , ring (chemistry) , thromboxane a synthase , in vitro , stereochemistry , thromboxane a2 , platelet , organic chemistry , biochemistry , receptor , materials science , immunology , metallurgy , biology
A series of ω‐carboalkenyl pyrazole derivatives have been synthesized as potential thromboxane‐synthetase inhibitors considering the close bioisosteric relationship between the pyrazole ring and other heteroaromatic carboalkenyl compounds exhibiting inhibitory activity. ( E )‐7‐(1‐Phenylpyrazol‐4‐yl)hept‐2‐enoic acid (4b) were prepared in 28% overall yield from its minor bis‐homologue, ( E )‐5‐(1‐phenylpyrazol‐4‐yl)pent‐2‐enoic acid (4a) , obtained from 4‐formyl‐1‐phenylpyrazole (6) in 17% overall yield. Compounds 4a, 4b, 7, 8 and 13 were screened for their ability to inhibit the in vitro rabbit blood platelet aggregation induced by collagen using the Born test. Among the active compounds 4a exhibited an important inhibition at 1 μ M concentration.