A series of novel pyrazole carboxylic acid derivatives was designed and synthesized, and their antagonism effect
on endothelin (ET)-1-induced contraction in the rat thoracic aortic ring was screened. The radio receptor assay was
used to examine the potency of the compounds on ET receptor. Some target compounds demonstrated significant inhibitory
activity, especially 7m, which showed a potent inhibition percentage higher than the contrast compound BQ123. Further
assays on the binding and selectivity for ET showed that 7m had highly potent binding activity on ETA at the nanomole
level, and the ratio of ETA/ETB was 36. Therefore, we inferred that 7m was a non-selective antagonist of ETA and
ETB and had potential for further development in cardiovascular diseases.
Keywords: Pyrazole acid, endothelin, antagonist, synthesis, BQ123, cardiovascular.
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Published on: 22 October, 2013
Page: [1113 - 1122]