Potential histamine H₂-receptor antagonists: synthesis and pharmacological activity of derivatives containing 3-alkylamino-4-amino-furazan moieties

A series of 3-alkylamino-4-(2-((5-dimethylaminomethyl-2-furyl)methylthio)ethylamino)furazans were prepared and tested for their H₂-antagonist activities on guinea pig right atrium. A number of differently shaped alkyl substituents on the terminal 3-amino group were favourable for activity. The most potent compound was the cyclohexyl-methyl-substituted derivative (pA₂=8.83). Most compounds showed non-competitive antagonism at histamine H₁ and muscarinic receptors at concentrations approximately 100 times higher than those producing competitive H₂-receptor block. This finding suggests that there is an accessorial binding area on H₂-receptor near the site fitted by the diamino-furazan moiety.