Design, synthesis and evaluation of antihypertensive activity of novel nitric oxide-releasing N-phenyl-1H-pyrrole derivatives / 中国药学杂志

ABSTRACT

OBJECTIVE: To synthesize and evaluate of antihypertensive activity of novel nitric oxide-releasing N-phenyl-1H-pyrrole derivatives. METHODS: By connecting key structural elements present in an AT1 receptor antagonist irbesartan with N-phenyl-1H-pyrrole carboxylic acid, a novel AT1 antagonist compound 4 was designed and synthesized, and a series of novel NO-donating derivatives (IN 1-10) were obtained by introducing NO donor. The amount of NO production in vitro of the target compounds were determined by Greiss assay. And the antagonism of Ang II induced vascular contraction assay was used to value the inhibition rate. RESULTS: The antagonism of Ang II induced vascular contraction assay indicated that the novel compound exhibited similar activity as losartan. The NO derivative, compound IN9, found to release the maximum amount of NO during the NO releasing assay, was more potent than the lead compound 4 and positive control losartan. CONCLUSION: These date indicate that the improved activities of these hybrid molecules contribute to the NO donor and the protection ability of NO donor make them promising candidates as antihypertensive agents.