Synthesis, Saludiuretic, and Antihypertensive Activity of 6,7-Disubstituted 1(2H)- and 3,4-Dihydro-1(2H)-phthalazinones

Article abstract of DOI:10.1021/jm00156a011

The synthesis of the isomeric series 6-chloro-7-sulfamoyl-and 7-chloro-6-sulfamoyl-1(2H)-phthalazinones (1 and 2) and 6-chloro-7-sulfamoyl- and 7-chloro-6-sulfamoyl-3,4-dihydro-1(2H)-phthalazinones (3 and 4), combining structural features characteristic to furosemide and hydralazine, is described, the mechanism of the formation of 1 and 2 is discussed, and their structure-activities relationships are studied.Preliminary screening in the rat shows that series 1 and 3 exhibit diuretic and saluretic activity similar to that of chlorothiazide with, however, Na⁺/K⁺ ratios more favorable than chlorothiazide and furosemide.The compounds of series 2 and 4 are practically inactive.All four series show initial antihypertensive activity lower than that of hydralazine.However, compounds 1a, 1c, and 4a show a higher activity at 8 and/ or 24 h after administration and thus may offer a unique combination of a "loop" diuresis with direct long-acting peripheral vasodilating effects.