NEW ANALOGS OF BURIMAMIDE AS POTENT AND SELECTIVE HISTAMINE H-3 RECEPTOR ANTAGONISTS - THE EFFECT OF CHAIN-LENGTH VARIATION OF THE ALKYL SPACER AND MODIFICATIONS OF THE N-THIOUREA SUBSTITUENT

Burimamide was one of the first compounds reported to antagonize the a ctivation of the histamine H-3 receptor by histamine. We have prepared a large series of burimamide analogs by variation of the alkyl spacer length of burimamide from two methylene groups to six methylene group s and also by replacement of the N-methyl group with other alkyl and a ryl groups. All analogs are reversible, competitive H-3 antagonists as determined on the guinea pig intestine. Elongation of the alkyl chain from an ethylene chain to a hexylene chain results in an increase of the H-3 antagonistic activity. The H-3 selective pentylene and hexylen e analogs of burimamide are about 10 times more potent than burimamide . The N-thiourea substituents, however, have no beneficial influence o n the affinity.