A study of the synthesis and antiarrhythmic properties of selected 3,7-diheterabicyclo[3.3.1]nonanes with substituents at the 2,4-positions and at the 9-position

Abstract

Some members of the family of 3,7-diheterabicyclo[3.3.1]nonanes with substituents at the 2-, 4- and 9-positions were synthesized via a Mannich reaction. Hearts of anesthetized dogs with myocardial infarctions were subjected to ventricular tachycardia (VT). Heterocyclics with [S, NR] or [RN, NR] at the 3- or 7-positions exhibited ability to abolish VT [or prevent the VT from being sustained] or reduce the rate of VT. A CH 2 group at the 9-position or the methyl ketal group [(H 3CO) 2C(9)] enhanced the antiarrhythmic activity regardless of whether sulfur or nitrogen was at the 3-position. Compounds with aryl groups alpha to the heteroatoms were less effective in controlling VT. Lidocaine was the standard.