Synthesis and activity of 1,4-dihydropyridine analogues of histamine H2-receptor antagonists.

Compounds of the type Het-CH 2 -S-CH 2 -CH 2 -Y were prepared, in which Het was 2-, 3- or 4-pyridyl, and Y was a derivative of 2-cyano-1,1-iminodiamine or 2-nitro-1,1-ethenediamine in which the terminal nitrogen was incorporated into a 1,4-dihydropyridine ring. Pharmacological testing using the histamine-induced guinea pig atrial chronotropic response indicated that the pyridyl substituent position was a determinant of activity, the activity order within each isomeric series being usually 2-pyridyl>3- and 4-pyridyl. In general, the incorporation of the terminal nitrogen into a 1,4-dihydropyridyl ring system favoured biological activity