NEW RYL-1,2,3,4-TETRAHYDROPYRIDO[2,3-D]PYRIMIDIN-4-ONE DERIVATIVES ASDIURETICS

2-Aryl-1,2,3,4-tetrahydropyrido [2,3-d]pyrimidin-4-one derivatives hav ing various substituents at the 4'-position, H or methyl at 1,3-positi ons and nitro or amino at 6-position were prepared and tested for thei r diuretic, natriuretic and kaliuretic activities on male Wistar rats at a dosage of 25 mg/kg or less. 2-(3-Pyridyl) derivatives were inacti ve. 1,3-Dimethyl-6-nitro-2-phenyl derivatives (1) were active dependin g on the electronic character of the 4'-substituent but at the same ti me were sodium-sparing However, 1(H),3(H)-6-nitro-2-phenyl derivatives (2) were generally inactive as diuretics but active as potassium-spar ing drugs. 6-Amino-1(H), 3(H)-2-phenyl derivatives (4) were active as diuretics depending on dipolar moment of the substituent at the 4'-pos ition, and induced moderate potassium release. The 6-amino-2- (4- trif luoromethylphenyl)- 1,2,3,4-tetrahydropyrido [2,3-d]pyrimidin-4-one (4 f) remained active up to a dosage of 3 mg/kg. The structure-activity r elationships were carried out in light of the adaptative least squares (ALS) method and discriminant functions for diuretic compounds were e stablished.