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, ETA and ETB, 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 ETA- and ETB-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 ETA 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 ETA receptors.