Breslin H J, Kukla M J, Tuman R W, Rebarchak M C, Bowden C R
Department of Chemical Research, R. W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477.
J Med Chem. 1993 May 28;36(11):1597-603. doi: 10.1021/jm00063a009.
Nitrogen heterocyclic carboximidamides, such as linogliride, 1a, have been shown to possess significant hypoglycemic activity and have shown clinical efficacy as potential antidiabetic agents. We evaluated the biological significance of the heterocyclic ring A of general structure 1, which has always been maintained in this class of compounds, by preparing acyclic compounds of general structure 2. Preliminary in vivo biological testing, i.e., the glucose tolerance test in rats, indicates that a number of the specific acyclic carboximidamides prepared, 6a-kk, possessed significant hypoglycemic activity often comparable to, and in some cases better than, the activity noted for our model compound, 1a. These results suggest that the heterocyclic ring A of 1 is not essential for hypoglycemic activity for this class of compounds.
