Synthesis and pharmacological activity of fluorescent histamine H2 receptor antagonists related to potentidine[]

Fluorescently labeled histamine H2 receptor antagonists were synthesized starting from N-cyano-N′-[3-(3-piperidin-1-ylmethylphenoxy)propyl]guanidines with an additional N″-ω-aminoalkyl substituent (chain lengths 2–8 methylene groups) or from 3-(3-piperidin-1-ylmethylphenoxy)propylamine. The primary amino group was derivatized with various fluorophores (fluorescein, acridine, dansyl, nitrobenzoxadiazole (NBD), indolo[2,3-a]quinolizine). On the isolated spontaneously beating guinea pig right atrium most of the fluorescent probes were only weakly active, however, the NBD-labeled substances proved to be potent histamine H2 receptor antagonists achieving pA2 values in the range of 7.5–8.0, comparable to the activity of famotidine.