Unsymmetrically substituted guanidines as potent histamine H3-receptor antagonists
Di- and trisubstituted guanidino derivatives of 4-(imidazoly)alkylamines are described as highly potent and selective histamine H3-receptor antagonists. The procedure of preparation with versatile synthons to result in differently substituted guanidines is given. N1-Cyclohexylmethyl-N2-[3-(1H-imidazol-4-yl)propyl]guanidine shows a Ki of 7.4x10−10M at H3-receptors and low activity at other histamine receptor sybtypes.
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Cited by (27)
Non-imidazole histamine H <inf>3</inf> ligands. Part III. New 4-n-propylpiperazines as non-imidazole histamine H <inf>3</inf>-antagonists
2005, European Journal of Medicinal ChemistryCitation Excerpt :However, histamine H3-receptors antagonists have not been introduced into therapy yet, but potential therapeutic applications have been proposed, e.g. memory and learning deficits [10–12], epilepsy [13,14], Alzheimer’s disease [15,16], and attention-deficit hyperactivity disorder [17]. Since the discovery of thioperamide (Ki = 4.3 nM) [18] (Chart 1), the prototype of H3-antagonist, many potent ligands carrying an imidazole moiety have been described [19–24] among others, potent and selective antagonists with high in vitro and in vivo activity FUB 470 [25] and ciproxifan [26] (Chart 1). The most representative compound of this group is GT 2331 (Ki = 0.12 nM) [27] (Chart 1); the first histamine H3-antagonist to be taken into human clinical trials.
Synthesis, biological activity, QSAR and QSPR study of 2- aminobenzimidazole derivatives as potent H<inf>3</inf>-antagonists
2004, Bioorganic and Medicinal Chemistry[3-(1H-Imidazol-4-yl)propyl]guanidines containing furoxan moieties: A new class of H<inf>3</inf>-antagonists endowed with NO-donor properties
2003, Bioorganic and Medicinal ChemistryCitation Excerpt :Analysis (C, H, N) of the new compounds was performed by REDOX (Monza). Structures 2,15 4, 5,16 7,23 9,24 13,25 14,26 15,17 1627 were synthesised according to reported methods. Following abbreviations are used: DMF, N,N-dimethylformamide; Et2O, diethyl ether; THF, tetrahydrofuran; DIAD, diisopropylazodicarboxylate; PE, petroleum ether 40–60 °C; AcOEt, ethyl acetate.
6 The Histamine H<inf>3</inf> Receptor and its Ligands
2001, Progress in Medicinal Chemistry