Piperidine-containing histamine H3 receptor antagonists of the carbamate series: the influence of the additional ether functionality.
Recently novel leads for histamine H3 receptor antagonists of the non-imidazole type have been described. As a continuation of this research eleven new carbamate derivatives possessing an additional ether functionality were prepared. The compounds were evaluated in vitro for their antagonist activity on isolated organs of guinea-pig (GP) H3 as well as H2, H1, and M3 receptors, respectively. All compounds investigated possessed moderate antagonist affinities at guinea-pig histamine H3 receptors (pA2 6.11-6.76). An ether functionality introduced in different places of the lipophilic part of carbamates differently influenced activity and selectivity toward H3, M3, and other histamine receptors tested.
Łazewska
D
D
Department of Chemical Technology of Drugs, Medical College, Jagiellonian University, Kraków, Poland.
Kieć-Kononowicz
K
K
Pertz
H H
HH
Elz
S
S
Stark
H
H
Schunack
W
W
D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis* / Q000494:pharmacology*; D004558:Electric Stimulation; D004987:Ethers / Q000737:chemistry; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D009119:Muscle Contraction / Q000187:drug effects; 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; D004987:Ethers; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D010880:Piperidines; D043587:Receptor, Muscarinic M3; D018100:Receptors, Histamine H3; D011976:Receptors, Muscarinic