2-(Aminomethyl)phenols, a new class of saluretic agents. 6. Effects of N,O-spiroannulation and subsequent quaternization

J Med Chem. 1983 Apr;26(4):585-90. doi: 10.1021/jm00358a024.

Abstract

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.

MeSH terms

  • Amines / pharmacology*
  • Animals
  • Benzylamines / pharmacology*
  • Blood Pressure / drug effects
  • Dogs
  • Rats
  • Sodium Chloride / urine

Substances

  • Amines
  • Benzylamines
  • Sodium Chloride
  • 2-(aminomethyl)phenol