| Abstract
| - Adrenomedullin (AM) is a peptide hormone implicated in blood pressure regulation and in thepathophysiology of several diseases such as hypertension, cancer, diabetes, and renal disorders,becoming an interesting new target for the development of drugs. In a recent high-throughputscreening study, a positive modulator with a bistriazole structure has been identified. In thiswork, a new series of structurally related compounds has been synthesized by reaction ofphenoxyacetic acid with the corresponding dihydrazide, followed by treatment of the formedbisoxadiazoles with benzylamine. The affinity toward AM of the lead compound, and astructurally related family obtained from the small-molecule NCI library together with thesynthesized series, has been determined. A three-dimensional quantitative structure−activityrelationship (3D-QSAR) study and conformational and molecular dynamics simulations haveshown that the presence of a free NH and a phenyl group is essential for the interaction ofthese compounds with AM.
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