Journal of Medicinal Chemistry · 1977 · 26 citations · 0 references
PharmacyMedicinal ChemistryPharmacologyDrug DiscoveryOrganic ChemistryStructure-activity RelationshipsDiuretic TherapyRenal PharmacologyStructure-activity Relationship AnalysisAmino Acid AmidesAmino Acid DerivativesDiuretic MechanismsFractional Excretion Of SodiumMedicinal Chemistry ApplicationsUrinary Sodium ExcretionUrine Volume Assessment
A variety of 2,3-disubstituted 5,7-dimethyl-1,8-naphthyridines was synthesized and tested in saline-loaded rats for their diuretic properties. The 2-amino-3-carbomethoxy and four 2-amino-3-N-alkylcarbamoyl compounds exhibited significant activity as measured by volume output; however, they were generally less potent than the corresponding 5,7-unsubstituted naphthyridines previously reported. Further screening without saline-loading indicated that the amides lacked kaliuretic properties; while, interestingly, the ester lacked an effect on either urine volume or sodium excretion.