New analogs of burimamide as potent and selective histamine H3 receptor antagonists: The effect of chain length variation of the alkyl spacer and modifications of the N-thiourea substituent

Article abstract of DOI:10.1021/jm00012a025

Burimamide was one of the first compounds reported to antagonize the activation of the histamine H₃ 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 groups and also by replacement of the N-methyl group with other alkyl and aryl groups. All analogs are reversible, competitive H₃ 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 H₃ antagonistic activity. The H₃ selective pentylene and hexylene analogs of burimamide are about 10 times more potent than burimamide. The N-thiourea substituents, however, have no beneficial influence on the affinity.