Novel (E)-α-[(1H-indol-3-yl)methylene]benzeneacetic acids as endothelin receptor ligands

Valeria Pittalà, Giuseppe Romeo, Luisa Materia, Loredana Salerno, Maria Angela Siracusa, Maria Modica, Ilario Mereghetti, Alfredo Cagnotto, Filippo Russo

Research output: Contribution to journalArticle

Abstract

Endothelin-1 (ET-1), a peptide of 21 amino acid residues, is the most potent vasoconstrictor substance known and now it is understood to be one of a family of three mammalian vasoactive peptides that also includes ET-2 and ET-3. The endothelins (ETs) affect multiple organ systems and seem to be involved in the pathogenesis of many diseases such as hypertension, pulmonary hypertension, atherosclerosis, apoptosis inhibition and angiogenesis. The ETs exert their effects via activation of two distinct G-protein coupled receptor subtypes termed ETA and ETB. To date a number of ET receptor ligands with good affinity and selectivity is known, nevertheless these compounds belong only to few chemical classes. The aim of this work was the identification of a "hit compound" with novel chemical structure, endowed with reasonable ET affinity and selectivity. Accordingly, a new class of (E)-α-[(1H-indol-3-yl)methylene]benzeneacetic acid derivatives (1-23) was synthesized for evaluation of their binding profiles.

Original languageEnglish
Pages (from-to)731-738
Number of pages8
JournalFarmaco
Volume60
Issue number9
DOIs
Publication statusPublished - Sep 2005

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Keywords

  • (E)-α-(1H-indol-3-ylmethylene)benzeneacetic acid derivatives
  • Endothelin receptors
  • G Protein-coupled receptors
  • Hypertension

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmaceutical Science

Cite this

Pittalà, V., Romeo, G., Materia, L., Salerno, L., Siracusa, M. A., Modica, M., Mereghetti, I., Cagnotto, A., & Russo, F. (2005). Novel (E)-α-[(1H-indol-3-yl)methylene]benzeneacetic acids as endothelin receptor ligands. Farmaco, 60(9), 731-738. https://doi.org/10.1016/j.farmac.2005.06.010