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.
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.
Vollinga
R C
RC
Leiden/Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit Amsterdam, The Netherlands.
Menge
W M
WM
Leurs
R
R
Timmerman
H
H
D000818:Animals; D002049:Burimamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D006168:Guinea Pigs; D006633:Histamine Antagonists; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D013890:Thiourea / Q000737:chemistry*
D006633:Histamine Antagonists; D013890:Thiourea; D002049:Burimamide