No abstract

Histamine has been converted into a non‐imidazole H3‐receptor histamine antagonist by addition of a 4‐phenylbutyl group at the Nα‐position followed by removal of the imidazole ring. The resulting compound, N‐ethyl‐N‐(4‐phenylbutyl)amine, remarkably has a Ki = 1.3 μM as an H3 antagonist. Using this as a lead compound, a novel series of homologous O and S isosteric tertiary amines was synthesised and structure‐activity studies furnished N‐(5‐phenoxypentyl)pyrrolidine (Ki = 0.18 ± 0.10 μM, for [3H]histamine release from rat cerebral cortex synaptosomes) which, more importantly, was active in vivo. Substitution of NO2 into the para position of the phenoxy group gave N‐(5‐p‐nitrophenoxypentyl)pyrrolidine, UCL 1972 (Ki = 39 ± 11 nM), ED50 = 1.1 ± 0.6 mg/kg per os in mice on brain tele‐methylhistamine levels.

No abstract

No abstract

No abstract