title: Synthesis and endothelin receptor binding affinity of a novel class of 2-substituted-4-aryl-3-quinolinecarboxylic acid derivatives.
abstract: The 21-amino acid peptide endothelin-1 (ET-1) is the predominant isoform of the endothelin peptide family, which includes ET-2, and ET-3. These peptides display a variety of physiological activities including vasoconstriction and the stimulation of cell proliferation in tissues both within and outside of the cardiovascular system. They exert their actions via activation of two distinct receptor subtypes, ET(A) and ET(B), belonging to the G protein-coupled receptor (GPCR) superfamily. Ligands of these receptors have received numerous citations in the recent pharmaceutical literature. In particular receptor antagonists, both ET(A)- and ET(B)-selective, as well as non-selective, have been described due to their wide therapeutic potential. As a part of our program toward the development of selective ET(A) ligands we have designed and we now report new molecules based on 2-substituted-4-aryl-3-quinolinecarboxylic acid moiety. Binding profile for some compounds (40, 44, 46, and 47) of this class showed a reasonable affinity and selectivity for ET(A) receptors.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Catania, Catania, Italy. vpittala@unict.it
authors.forename: Valeria
authors.initials: V
authors.lastname: Pittalà
authors.forename: Maria
authors.initials: M
authors.lastname: Modica
authors.forename: Loredana
authors.initials: L
authors.lastname: Salerno
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Siracusa
authors.forename: Francesco
authors.initials: F
authors.lastname: Guerrera
authors.forename: Ilario
authors.initials: I
authors.lastname: Mereghetti
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cagnotto
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mennini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Romeo
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry*; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D008024:Ligands; D011804:Quinolines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin