Synthesis and conformational analysis of Substance P antagonist analogues based on a 1,7-naphthyridine scaffold

Two analogues of formerly described piperidine-based Substance P antagonists have been synthesised using an intramolecular Diels–Alder reaction of 1-(4-pentenyl)-3-phenyl-2(1H)-pyrazinones, followed by acidic methanolysis of the strained adducts to form the 8-oxo-6-phenyldecahydro [1,7]-naphthyridine-6-carboxylate esters and further conversion to the corresponding O-benzyl substituted 6-(hydroxymethyl) target compounds. Conformational analyses of intermediates and the final products are presented, based on 1H NMR and modelling data.