2-(Aminomethyl)phenols, a new class of saluretic agents. 6. Effects of N,O-spiroannulation and subsequent quaternization.
The synthesis of a number of 3,4-dihydrospiro-2H-1,3-benzoxazines and their corresponding benzoxazinium salts are reported. The saluretic effects displayed by these N,O-spiroannulated 2-(aminomethyl)phenols appear to be, in part, inversely related to their respective in vivo rates of hydrolysis. Good antihypertensive effects are found only in spirobenzoxazinium 22. Thus, a combination of spiroannulation and quaternization on 2 to produce 22 leads to a loss of saluretic effects with maintenance of antihypertensive effects and, thereby, serves to separate these pharmacological properties.
D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D051381:Rats; D012965:Sodium Chloride / Q000652:urine
D000588:Amines; D001596:Benzylamines; D012965:Sodium Chloride; C032416:2-(aminomethyl)phenol