Substituted 2,4-diaminoquinazolines and 2,4-diamino-8-alkylpurines as antagonists of the neurokinin-2 (NK2) receptor

Nonpeptidic Ligands for Peptide-Activated G Protein-Coupled Receptors

“…Compound 425 reported by Zenica was the most potent member of a series of pyrrolopyrimidines that competitively inhibited [ 3 H]NKA binding to hamster urinary bladder NK2 receptors ( K i 2 nM) and showed good selectivity over NK1 receptors ( K i 2 μM inhibition of [ 3 H]SP binding to NK1 receptors in guinea pig lung membranes). Because of a substantial species selectivity difference, 425 was 48-fold weaker for inhibition of NKA binding in cloned human NK1 receptors and was 90-fold less potent as a competitive antagonist of NKA-induced contractile responses in human bronchus. , …”

“…Because of a substantial species selectivity difference, 425 was 48-fold weaker for inhibition of NKA binding in cloned human NK1 receptors and was 90-fold less potent as a competitive antagonist of NKA-induced contractile responses in human bronchus. 400 receptor subtypes (Y1-Y6). Additionally, there are two closely related peptides that share a common C-terminal amino acid sequence, termed peptide YY (PYY) and pancreatic peptide (PP) that are also ligands for these receptors.…”