Details

Autor(en) / Beteiligte

• Dvorak, Curt A
• Apodaca, Richard
• Barbier, Ann J
• Berridge, Craig W
• Wilson, Sandy J
• Boggs, Jamin D
• Xiao, Wei
• Lovenberg, Timothy W
• Carruthers, Nicholas I

Titel

4-Phenoxypiperidines:  Potent, Conformationally Restricted, Non-Imidazole Histamine H3 Antagonists

Ist Teil von

• Journal of medicinal chemistry, 2005-03, Vol.48 (6), p.2229-2238

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

2005

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Two new series of 4-(1-alkyl-piperidin-4-yloxy)-benzonitriles and 4-(1-isopropyl-piperidin-4-yloxy)-benzylamines have been prepared. In vitro activity was determined at the recombinant human H3 receptor and several members of these new series were found to be potent H3 antagonists. The present compounds contain a 4-phenoxypiperidine core, which behaves as a conformationally restricted version of the 3-amino-1-propanol moiety common to the many previously described non-imidazole histamine H3 ligands. One selected member of the new series, 4-[4-(1-isopropyl-piperidin-4-yloxy)-benzyl]-morpholine (13g), was found to be a potent, highly selective H3 receptor antagonist with in vivo efficacy in a rat EEG model of wakefulness at doses as low as 1 mg/kg sc.