New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidine derivatives as diuretics.
New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidines 1 and 6,10-dihydro-5H-pyrido[3',2':5,6]pyrimido[2,1-c] [1,2,4]triazines 4 with 5-one, 5-thione or 5-hydrazono substituents and in some cases 1,2,3,4 or 8,9 hydrogenated are synthetized. The diuretic, natriuretic and kaliuretic activities of these compounds in Wistar rats at a dose of 24 mg/kg were estimated. A series of 24 possible derivatives of 1 and 4 possessing diuretic and saliuretic activities are investigated for structure-activity relationships in light of Fujita-Ban model. The Fujita-Ban group contributions have been calculated for different structural variations on the parent ring 1a. It is observed that the hydrogenation of pyridine, [1,3]thiazole or [1,2,4]triazine rings on 1 or 4 decrease the diuretic and saliuretic activities.
Monge
A
A
Centro de Investigación en Farmacobiología Aplicada (C.I.F.A.), Universidad de Navarra, Pamplona, Spain.
Martinez-Merino
V
V
Sanmartin
C
C
Ochoa
M C
MC
Fernandez-Alvarez
E
E
D000818:Animals; D004232:Diuretics / Q000138:chemical synthesis*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D004232:Diuretics; D011725:Pyridines; D011743:Pyrimidines; D013844:Thiazoles; D011188:Potassium