New 1‐Benzyl‐4‐hydroxypiperidine Derivatives as Non‐imidazole Histamine H3 Receptor Antagonists |
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| Authors: | Iwona Maslowska‐Lipowicz Marek Figlus Obbe P. Zuiderveld Krzysztof Walczynski |
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| Affiliation: | 1. Department of Synthesis and Technology of Drugs, Medical University, Lódz, Poland. Fax: +48 42 6779159;2. Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Vrije Universiteit, Amsterdam, The Netherlands |
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| Abstract: | 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 H3 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 (hH3R, pKi = 7.09), 9b1 (hH3R, pKi = 6.78), 9b5 (hH3R, pKi = 6.99), and 9b6 (hH3R, pKi = 6.97) were also tested in vitro as H3 receptor antagonists – the electrically evoked contraction of the guinea‐pig jejunum. The histaminergic H1 antagonism of selected compounds 9b1 , 9b2 , and 9b4 – 9b6 was established on the isolated guinea‐pig ileum by conventional methods; the pA2 values were compared with the potency of pyrilamine. The compounds did not show any H1 antagonistic activity (pA2 < 4; for pyrilamine pA2 = 9.53). |
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| Keywords: | 1‐Benzyl‐4‐(3‐aminopropyloxy)piperidine 1‐Benzyl‐4‐(5‐aminopentyloxy)piperidine derivatives H3 antagonists Histamine H3 receptor |
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