Detail of "9029-80-5"

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Search for histamine H3 receptor ligands with combined inhibitory potency at histamine N-methyltransferase: w-piperidinoalkanamine derivatives

Search for histamine H3 receptor ligands with combined inhibitory potency at histamine N-methyltransferase: w-piperidinoalkanamine derivatives. Grassmann, Sven; Apelt, Joachim; Ligneau, Xavier; Pertz, Heinz H.; Arrang, Jean-Michel; Ganellin, C. Robin; Schwartz, Jean-Charles; Schunack, Walter; Stark, Holger (Institut fuer Pharmazie, Freie Universitaet Berlin, Berlin, Germany). Archiv der Pharmazie (Weinheim, Germany), 337(10), 533-545 (English) 2004 Wiley-VCH Verlag GmbH & Co. KGaA. CODEN: ARPMAS. ISSN: 0365-6233. DOCUMENT TYPE: Journal CA Section: 27 (Heterocyclic Compounds (One Hetero Atom)) Section cross-reference(s): 1 In an effort to design new hybrid compds. with dual properties, i.e. binding affinity at histamine H3 receptors and inhibitory potency at the catabolic enzyme histamine Nt-methyltransferase (HMT), a novel series of 1-substituted piperidine derivs. was synthesized. This alicyclic heterocycle is structurally linked via aminoalkyl spacers of variable lengths to addnl. arom. carbo- or heterocycles. These new hybrid drugs were pharmacol. evaluated regarding their binding affinities at recombinant human H3 receptors, stably expressed in CHO cells, and in a functional assay for their inhibitory potencies at rat kidney HMT. All compds. investigated proved to be H3 receptor ligands with binding affinities in the micro- to nanomolar concn. range despite significant differences in the type of the arom. moiety introduced. The most potent compd. in this series was I [n = 5, R1 = Me, R2 = quinolin-4-yl] (Ki = 5.6 nM). Likewise, all new ligands studied showed impressive HMT inhibitory activities, I [n = 3, 5, R1 = H, R2 = 5-amino-2-pyridinyl; n = 6, R1 = H, R2 = 2-pyrimidinyl; n = 2, 4, 5, R1 = Me, R2 = 4-pyridinyl, 4-quinolinyl] exhibiting submicromolar potencies (IC50 = 0.061-0.56 mM).In this study，9029-80-5 is also used. I [n = 4, R1 = Me, R2 = 4-quinolinyl] showed almost the same, well balanced nanomolar activities on both targets. .