152030-50-7Relevant articles and documents
A novel series of (phenoxyalkyl)imidazoles as potent H3-receptor histamine antagonists
Ganellin, C. Robin,Fkyerat, Abdellatif,Bang-Andersen, Benny,Athmani, Salah,Tertiuk, Wasyl,Garbarg, Monique,Ligneau, Xavier,Schwartz, Jean-Charles
, p. 3806 - 3813 (2007/10/03)
[[(4-Nitrophenyl)X]alkyl]imidazole isosteres (where X = NH, S, CH2S, O) of previously described [[(5-nitropyrid-2-yl)X]ethyl]imidazoles (where X = NH, S) have been synthesized and evaluated for H3-receptor histamine antagonism in vitro (K(i) for [3H]histamine release from rat cerebral cortex synaptosomes) and in vivo (ED50 per os in mice on brain tele- methylhistamine levels). Encouraging results led to the synthesis and testing of a novel series of substituted (phenoxyethyl)- and (phenoxypropyl)imidazoles. From the latter, 4-[3-(4-cyanophenoxy)propyl]-1H- imidazole (10a, UCL 1390; K(i) = 12 nM, ED50 = 0.54 mg/kg) and 4-[3-[4- (trifluoromethyl)-phenoxy]propyl]-1H-imidazole (10c, UCL 1409; K(i) = 14 nM, ED50 = 0.60 mg/kg) have been selected as potential candidates for drug development. For 16 [(aryloxy)ethyl]imidazoles the relationship between in vitro and in vivo potency is described by the equation log ED50 = 0.47 log K(i) + 0.20 (r = 0.78).
