Alkyl derivatives of 1,3,5-triazine as histamine H4 receptor ligands |
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| Authors: | Dorota Łażewska Szczepan Mogilski Stefanie Hagenow Kamil Kuder Monika Głuch-Lutwin Agata Siwek Małgorzata Więcek Maria Kaleta Ulla Seibel Armin Buschauer Barbara Filipek Holger Stark Katarzyna Kieć-Kononowicz |
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| Affiliation: | 1. Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, ul. Medyczna 9, 30-688 Kraków, Poland;2. Department of Pharmacodynamic, Faculty of Pharmacy, Jagiellonian University Medical College, ul. Medyczna 9, 30-688 Kraków, Poland;3. Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany;4. Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, ul. Medyczna 9, 30-688 Kraków, Poland;5. Department of Pharmaceutical/Medicinal Chemistry, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany |
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| Abstract: | This study focuses on the design, synthesis, molecular modeling and biological evaluation of a novel group of alkyl-1,3,5-triazinyl-methylpiperazines. New compounds were synthesized and their affinities for human histamine H4 receptor (hH4R) were evaluated. Among them, 4-(cyclohexylmethyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (14) exhibited hH4R affinity with a Ki of 160?nM and behaved as antagonist in functional assays: the cellular aequorin-based assay (IC50?=?32?nM) and [35S]GTPγS binding assay (pKb?=?6.67). In addition, antinociceptive activity of 14 in vivo was observed in Formalin test (in mice) and in Carrageenan-induced acute inflammation test (in rats). |
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| Keywords: | 1,3,5-Triazine Docking Pain |
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