New 1-benzyl-4-hydroxypiperidine derivatives as non-imidazole histamine H3 receptor antagonists.
A series of 1-benzyl-4-(3-aminopropyloxy)piperidine and 1-benzyl-4-(5-aminopentyloxy)piperidine derivatives has been prepared. The 1-benzyl-4-hydroxypiperidine derivatives obtained were evaluated for their affinities at recombinant human histamine H(3 )receptor, stably expressed in HEK 293T cells. All compounds investigated show moderate to pronounced in-vitro affinities. The most potent antagonists in this series 9b2 (hH(3)R, pK(i) = 7.09), 9b1 (hH(3)R, pK(i) = 6.78), 9b5 (hH(3)R, pK(i) = 6.99), and 9b6 (hH(3)R, pK(i )= 6.97) were also tested in vitro as H(3 )receptor antagonists - the electrically evoked contraction of the guinea-pig jejunum. The histaminergic H(1) antagonism of selected compounds 9b1, 9b2, and 9b4-9b6 was established on the isolated guinea-pig ileum by conventional methods; the pA(2) values were compared with the potency of pyrilamine. The compounds did not show any H(1) antagonistic activity (pA(2) < 4; for pyrilamine pA(2) = 9.53).
Maslowska-Lipowicz
Iwona
I
Department of Synthesis and Technology of Drugs, Medical University, Lódz, Poland.
Figlus
Marek
M
Zuiderveld
Obbe P
OP
Walczynski
Krzysztof
K
D000818:Animals; D002460:Cell Line; D006168:Guinea Pigs; D054828:Histamine H3 Antagonists / Q000737:chemistry*; D006801:Humans; D007082:Ileum / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D054828:Histamine H3 Antagonists; D010880:Piperidines; D018100:Receptors, Histamine H3