Abstract:
:Adrenomedullin (AM) is a peptide hormone implicated in blood pressure regulation and in the pathophysiology 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-throughput screening study, a positive modulator with a bistriazole structure has been identified.(1) In this work, a new series of structurally related compounds has been synthesized by reaction of phenoxyacetic acid with the corresponding dihydrazide, followed by treatment of the formed bisoxadiazoles with benzylamine. The affinity toward AM of the lead compound, and a structurally related family obtained from the small-molecule NCI library together with the synthesized series, has been determined. A three-dimensional quantitative structure-activity relationship (3D-QSAR) study and conformational and molecular dynamics simulations have shown that the presence of a free NH and a phenyl group is essential for the interaction of these compounds with AM.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
García MA,Martín-Santamaría S,Cacho M,de la Llave FM,Julián M,Martínez A,de Pascual-Teresa B,Ramos Adoi
10.1021/jm050021+keywords:
subject
Has Abstractpub_date
2005-06-16 00:00:00pages
4068-75issue
12eissn
0022-2623issn
1520-4804journal_volume
48pub_type
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