Chemical and Pharmaceutical Bulletin · 1984 · 10 citations · 0 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignOrganic ChemistryStructure-activity RelationshipsEnzyme InhibitionHeterocyclic ChemistryQuantitative Structure-activity RelationshipsStructure-activity Relationship AnalysisChemical Structure-activity RelationshipsMedicinal HeterocyclesMolecular Orbital AnalysisNystagmus CharacterizationPyridine ChemistrySpontaneous Nystagmus
A number of 6-substituted 5, 6, 7, 8-tetrahydro-1, 6-naphthyridines designed as cyclic homologues of betahistine, 2-(2-methylaminoethyl) pyridine, were synthesized by the reduction of the corresponding 1, 6-naphthyridinium salts. The antivertigo activity of these derivatives was evaluated in terms of their ability to inhibit spontaneous nystagmus in cats. The relationships between the molecular structures of the test compounds and their antivertigo activities were investigated by a regression analysis based on the lipophilicity (π) of the substituents at the 6-position and by a conformational analysis of the compounds of interest using the modified neglect of diatomic overlap molecular orbital method. Among these compounds, the 6-allyl-and 6-cyclopropylmethyl derivatives exhibited extremely potent activity with greatly reduced hypotensive action.