Histamine H2-receptor blocking activity of ranitidine and lamtidine analogues containing aminomethyl-substituted...

The possibility that the aromatic component in the classical H2-antagonists might not be essential for histamine H2-receptor blockade has been investigated. In the ranitidine series the removal of the furan ring is accompanied by a drastic decrease in H2-blocking activity, but not by its disappearance (compound HB5:KB on guinea pig isolated atria 31.6 microM) whereas in the lamtidine analogues the substitution of the phenyl moiety with the more reduced pi-bonded CH3-C = N-area generates a compound whose activity is comparable to that of cimetidine (KB on atria 1.12 microM; ID50 in the lumen-perfused stomach of the anaesthetized rat 3.61 mumol/kg i.v.). The results also indicate that the diaminofurazan group confers high affinity at the histamine H2-receptor. It is concluded that the aromatic portion of H2-antagonists related to ranitidine and lamtidine is not a minimal requisite for activity when an appropriate polar group is used as an "urea equivalent" moiety.