Histamine analogues. 36th communication. Basically substituted histamine derivatives with H1-agonistic activity.
Piperidinoalkyl-, morpholinoalkyl- or [(pyrid-2-yl)methylthio]alkyl-substituents were introduced into position 2 of the essential histamine structure. These 2-substituted histamine derivatives were prepared via reaction of imidate hydrochlorides in liquid ammonia under pressure with 1,3-dihydroxypropanone followed by a stepwise build-up of the side chain in position 4 of the imidazole nucleus (route I) or by cyclization with 2-oxo-4-phthalimido-1-butyl acetate (route II) followed by deprotection of the primary amine function. The novel compounds were screened for H1-activity on the isolated guinea-pig ileum and for H2-activity on the isolated guinea-pig right atrium. While 10a, c-e proved to be weak partial H1-agonists, 10b, f were very weak H1-antagonists.
Zingel
V
V
Institut für Pharmazie, Freien Universität Berlin.
Elz
S
S
Schunack
W
W
D000818:Animals; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006632:Histamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017442:Histamine Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D013329:Structure-Activity Relationship
D017442:Histamine Agonists; D006632:Histamine