Novel (E)-alpha-[(1H-indol-3-yl)methylene]benzeneacetic acids as endothelin receptor ligands.
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.
Pittalà
Valeria
V
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Catania, viale A. Doria 6, 95125 Catania, Italy. vpittala@unict.it
Romeo
Giuseppe
G
Materia
Luisa
L
Salerno
Loredana
L
Siracusa
Maria Angela
MA
Modica
Maria
M
Mereghetti
Ilario
I
Cagnotto
Alfredo
A
Russo
Filippo
F
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
D008024:Ligands; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D011994:Recombinant Proteins; D019342:Acetic Acid