Histamine analogues, XXXV: 2-substituted histamine derivatives containing classical moieties of H2-antagonists--a novel class of H1-agonists.
A new type of H1-agonists resulted from the combination of the essential histamine structure with parts of H2-antagonists. 2,4-Disubstituted imidazole derivatives were synthesized by reaction of imidic acid methyl esters with 1,3-dihydroxypropanone, 1,4-dihydroxybutanone or 2-oxo-4-phthalimido-1-butylacetate in liquid NH3. The imidazole intermediates were converted into histamine analogues by simple deprotection, Gabriel synthesis followed by deprotection, or by side-chain elongation via the nitriles and final hydrogenation. The new compounds were screened for H1-activity on the isolated guinea-pig ileum and for H2-antagonistic activity on the isolated guinea-pig right atrium. The substances are comparably weak H1-agonists and moderate H2-blockers.
Zingel
V
V
Institut für Pharmazie der Freien Universität Berlin, Germany.
Elz
S
S
Schunack
W
W
D000818:Animals; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006632:Histamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D017442:Histamine Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects; D013329:Structure-Activity Relationship
D017442:Histamine Agonists; D006635:Histamine H2 Antagonists; D006632:Histamine