112357-34-3Relevant academic research and scientific papers
Synthesis and histamine H2-receptor activity of heterocyclic impromidine analogues.
Buschauer,Lachenmayr,Schunack
, p. 86 - 91 (2007/10/02)
Analogues of the H2-agonist impromidine with unsubstituted or substituted aromatic or non-aromatic heterocycles instead of the 5-methylimidazole group were prepared via the benzoylguanidine method and tested for H2-agonistic and H1-antagonistic activity in the guinea-pig isolated right atrium and ileum, respectively. Compounds with unsubstituted 2- or 3-pyridyl, 2-pyrazinyl, or 5-pyrimidyl thioether portion proved to be about equipotent in the atrium (about 2-4x histamine). Highest potency was found in the 5-chloro-3-pyridylthioethylguanidine 8h, that is about 20 times more potent as an H2-agonist than histamine, corresponding to about 8 times the activity of the unsubstituted parent compound 8g. It is demonstrated by the piperidinyl- and morpholinylalkyl guanidines 8m-o that an aromatic ring is not required in the affinity-conferring moiety of H2-agonists (8n: 1.3x histamine). Replacement of the (5-methylimidazol-4-yl)methylthio group in the H2-antagonist cimetidine by halogenated pyridyl, pyrazinyl and pyrimidinyl thioethers resulted in compounds inactive as H2-antagonists, giving further evidence for differences in the structural requirements of the affinity-conferring portions of H2-agonists and antagonists and their mode of interaction with the receptor protein.
An Alternative Synthesis of Homohistamine and Structurally Related (Imidazole-4-yl)alkylamines
Elz, Sigurd,Schunack, Walter
, p. 238 - 242 (2007/10/02)
Bromination of N-(4-oxopentyl)phthalimide (3) leads to isomeric bromoketones 2a and 2e, which undergo cyclisation with formamidine in liquid ammonia to yield homohistamine (1a) and 5-methylhistamine (1e).Similarly racemic α-methyl- (1b) and 2-methylhomohistamine (1c) are synthesized.The resolution of 1b is achieved using (+)- and (-)-di-O-(4-toluoyl)tartaric acid. 1 are intermediates in the synthesis of impromidine like, H2-histaminergic compounds. - Key words: Bromination of Methylketones, Halomethylketones, Histamine H2-Agonists, Homohistamine, Chiral Aminoalkylimidazoles
