Document Report Card

ID: ALA1136744

Journal: J Med Chem

Title: Synthesis and activity of substituted 2-phenylquinolin-4-amines, antagonists of immunostimulatory CpG-oligodeoxynucleotides.

Authors: Strekowski L, Say M, Henary M, Ruiz P, Manzel L, Macfarlane DE, Bojarski AJ.

Abstract: Fifty-seven 2-phenylquinolines substituted at the phenyl group and C4 of the quinoline were synthesized and analyzed for inhibition of the immunostimulatory effect of oligodeoxynucleotides with a CpG-motif. The Fujita-Ban variant of the classical Free-Wilson analysis gave a highly significant correlation for a series of 48 relatively small molecules demonstrating that (i) the partial contributions of substituents to biological activity (EC(50)) are additive and (ii) assuming similar bioavailability for all quinolines studied, the larger molecules cannot be accommodated within a still unknown biological receptor. The results suggest interaction of a basic antagonist molecule with weakly acidic groups in the antagonist-receptor complex. N-[2-(Dimethylamino)ethyl]-2-[4-(4-methylpiperazino)phenyl]quinolin-4-amine (50) is the most effective antagonist found in this study (EC(50) = 0.76 nM).

CiteXplore: 12646034

DOI: 10.1021/jm020374y