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Conformational restriction and enantioseparation increase potency and selectivity of cyanoguanidine-type histamine H4 receptor agonists

Geyer, Roland ; Nordemann, Uwe ; Strasser, Andrea ; Wittmann, Hans-Joachim ; Buschauer, Armin



Abstract

2-Cyano-1-[4-(1H-imidazol-4-yl)butyl]-3-[2-(phenylsulfanypethyl]guanidine (UR-PI376, 1) is a potent and selective agonist of the human histamine H-4 receptor (hH(4)R). To gain information on the active conformation, we synthesized analogues of 1 with a cyclopentane-1,3-diyl linker. Affinities and functional activities were determined at 'recombinant hH(X)R (x: 1-4) subtypes on Sf9 cell membranes ...

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