title: Novel (E)-alpha-[(1H-indol-3-yl)methylene]benzeneacetic acids as endothelin receptor ligands.
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 ET(A) and ET(B). 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)-alpha-[(1H-indol-3-yl)methylene]benzeneacetic acid derivatives (1-23) was synthesized for evaluation of their binding profiles.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Catania, viale A. Doria 6, 95125 Catania, Italy. vpittala@unict.it
authors.forename: Valeria
authors.initials: V
authors.lastname: Pittalà
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Romeo
authors.forename: Luisa
authors.initials: L
authors.lastname: Materia
authors.forename: Loredana
authors.initials: L
authors.lastname: Salerno
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Siracusa
authors.forename: Maria
authors.initials: M
authors.lastname: Modica
authors.forename: Ilario
authors.initials: I
authors.lastname: Mereghetti
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cagnotto
authors.forename: Filippo
authors.initials: F
authors.lastname: Russo
mesh_terms: D019342:Acetic Acid / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D044022:Receptor, Endothelin A / Q000187:drug effects*; D044023:Receptor, Endothelin B / Q000187:drug effects*; D011994:Recombinant Proteins / Q000187:drug effects; D013055:Spectrophotometry, Infrared
chemical_list: D008024:Ligands; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D011994:Recombinant Proteins; D019342:Acetic Acid