NEW POTENT HISTAMINE H-3 RECEPTOR ANTAGONISTS OF THE AMIDE TYPE

A new class of histamine H-3-receptor antagonists is described. Struct ure-activity relationships of amides show essential and non-essential, but affinity increasing structural requirements by example of 27 diff erent imidazole derivatives. The most potent compound in this series i s lopentyl-N-[3-(1H-imidazol-4-yl)propyl]propanamide (18, -log K-i = 8 .3) which is equipotent to the reference antagonist thioperamide (Arra ng et al., 1987) and shows high selectivity to the histamine H-3-recep tor. New amides with different chain length and different lipophilic m oieties are investigated. A number of compounds are similarly potent a s compound 18. Structural requirements of antagonists interacting with the H-3-receptor are discussed. In general, these new amides of the i midazolylalkyl type are potent and selective histamine H-3-receptor an tagonists.