Piperidine variations in search for non-imidazole histamine H(3) receptor ligands.
Synthesis and biological evaluation of the novel histamine H(3) receptor ligands is described. Two series of ethers (aliphatic and aromatic) have been prepared by four different methods. Compounds were evaluated for their affinities at recombinant human H(3) receptor stably expressed in CHO cells. The ethers show from low to moderate in vitro affinities in nanomolar concentration range. The most potent compound was the 1-[3-(4-tert-butylphenoxy)propyl]-4-piperidino-piperidine 16 (hH(3)R K(i)=100 nM). Several members of the new series investigated under in vivo conditions, proved to be inactive.
Łazewska
Dorota
D
Jagiellonian University Medical College, Faculty of Pharmacy, Department of Technology and Biotechnology of Drugs, Medyczna 9, 30-688 Kraków, Poland.
Kuder
Kamil
K
Ligneau
Xavier
X
Schwartz
Jean-Charles
JC
Schunack
Walter
W
Stark
Holger
H
Kieć-Kononowicz
Katarzyna
K
D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
C533358:1-(3-(4-tert-butylphenoxy)propyl)-4-piperidino-piperidine; D007093:Imidazoles; D008024:Ligands; D010880:Piperidines; D018100:Receptors, Histamine H3; C029899:imidazole