title: A facile synthesis of new 2-carboxamido-3-carboxythiophene and 4,5,6,7-tetrahydro-2-carboxamido-3-carboxythieno[2,3-c]pyridine derivatives as potential endothelin receptors ligands.
abstract: Endothelins (ETs) are the most ubiquitous, highly potent and unusually long-lasting peptidic constrictors of human vessels known. Elevated levels of the plasma concentration of ETs were observed in several diseases such as hypertension, acute myocardial infarction, congestive heart failure, renal failure, pulmonary hypertension, and atherosclerosis. ETs exert their activities via specific seven-transmembrane, G protein-coupled receptors. To date two receptor subtypes, endothelin A (ET(A)) and endothelin B (ET(B)), have been identified and cloned. A literature survey revealed that a number of compounds that bind ET receptors with affinity and selectivity are known, nevertheless these compounds belong only to few chemical classes. The aim of this work is the identification of an "hit compound" with novel chemical structure endowed with reasonable ET affinity and selectivity. Accordingly, new variously substituted 2-carboxamido-3-carboxythiophene derivatives (29-52) were synthesized. These compounds were tested for their ability to inhibit ETs binding in radioligand binding assay using CHO cells stably expressing human ET(A) and ET(B) receptors.
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: Maria
authors.initials: M
authors.lastname: Modica
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: Mariangela
authors.initials: M
authors.lastname: Siracusa
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cagnotto
authors.forename: Ilario
authors.initials: I
authors.lastname: Mereghetti
authors.forename: Filippo
authors.initials: F
authors.lastname: Russo
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D044022:Receptor, Endothelin A / Q000187:drug effects*; D044023:Receptor, Endothelin B / Q000187:drug effects*; D017466:Receptors, Endothelin / Q000187:drug effects*; D011994:Recombinant Proteins / Q000187:drug effects; D013055:Spectrophotometry, Infrared
chemical_list: D008024:Ligands; D011725:Pyridines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D011994:Recombinant Proteins