Piperidine-containing histamine H3-receptor antagonists of the carbamate series: variation of the spacer length.
Ten carbamate derivatives have been prepared from appropriate isocyanates and omega-piperidino-1-alkanols. All compounds belong to the new generation of non-imidazole histamine H3-receptor ligands which may have beneficial pharmacokinetic properties compared with the classical imidazole-containing H3-receptor antagonists. The carbamates were evaluated in vitro for antagonist activity at guinea-pig (gp) H3, H2, H1, and M3 receptors, respectively. They displayed moderate affinity for H3 receptors (pA2 5.8-7.0 in the gp ileum assay) as well as low to moderate selectivities vis-à-vis H2 (gp atrium), H1 (gp ileum), and M3 (gp ileum) receptors. A typical member of this series is 7-piperidino-1-heptyl N-(4-phenyl-1-butyl)carbamate (17) with pA2 values of 7.02 (H3), 5.92 (H1), and 6.38 (M3), respectively, and a pD'2 value of 5.46 (H2).
Łazewska
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Department of Chemical Technology of Drugs, Medical College, Jagiellonian University, Kraków, Poland.
Kieć-Kononowicz
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Pertz
H H
HH
Stark
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Schunack
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W
Elz
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D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D043587:Receptor, Muscarinic M3; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects; D013329:Structure-Activity Relationship
D002219:Carbamates; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007202:Indicators and Reagents; D008024:Ligands; D018727:Muscarinic Antagonists; D010880:Piperidines; D043587:Receptor, Muscarinic M3; D018100:Receptors, Histamine H3; D011976:Receptors, Muscarinic