Design, Synthesis, and Bioactivity of Pyrazole Acid Derivatives as Endothelin Receptor Antagonists

Title:Design, Synthesis, and Bioactivity of Pyrazole Acid Derivatives as Endothelin Receptor Antagonists

Volume: 9 Issue: 8

Author(s): Jin Cai, Ligang Liu, Junqing Chen, Meng Cao and Min Ji

Affiliation:

Keywords: Pyrazole acid, endothelin, antagonist, synthesis, BQ123, cardiovascular.

Abstract: 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 ET_A/ET_B was 36. Therefore, we inferred that 7m was a non-selective antagonist of ET_A and ET_B and had potential for further development in cardiovascular diseases.

Cite this article as:

Cai Jin, Liu Ligang, Chen Junqing, Cao Meng and Ji Min, Design, Synthesis, and Bioactivity of Pyrazole Acid Derivatives as Endothelin Receptor Antagonists, Medicinal Chemistry 2013; 9 (8) . https://dx.doi.org/10.2174/1573406411309080013