Discovery and pharmacological profile of new hydrophilic 5-HT(4) receptor antagonists.

Autor: Brudeli B; Drug Discovery Laboratory AS, Oslo Innovation Center, N-0349 Oslo, Norway; Department of Medicinal Chemistry, School of Pharmacy, University of Oslo, PO Box 1068 Blindern, N-0316 Oslo, Norway., Navaratnarajah M; Department of Pharmacology, Faculty of Medicine, University of Oslo and Oslo University Hospital, PO Box 1057 Blindern, N-0316 Oslo, Norway; Department of Medicinal Chemistry, School of Pharmacy, University of Oslo, PO Box 1068 Blindern, N-0316 Oslo, Norway., Andressen KW; Department of Pharmacology, Faculty of Medicine, University of Oslo and Oslo University Hospital, PO Box 1057 Blindern, N-0316 Oslo, Norway; K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Faculty of Medicine, University of Oslo, Norway., Manfra O; Department of Pharmacology, Faculty of Medicine, University of Oslo and Oslo University Hospital, PO Box 1057 Blindern, N-0316 Oslo, Norway; K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Faculty of Medicine, University of Oslo, Norway., Moltzau LR; Department of Pharmacology, Faculty of Medicine, University of Oslo and Oslo University Hospital, PO Box 1057 Blindern, N-0316 Oslo, Norway; K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Faculty of Medicine, University of Oslo, Norway., Nilsen NO; Drug Discovery Laboratory AS, Oslo Innovation Center, N-0349 Oslo, Norway., Levy FO; Department of Pharmacology, Faculty of Medicine, University of Oslo and Oslo University Hospital, PO Box 1057 Blindern, N-0316 Oslo, Norway; K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Faculty of Medicine, University of Oslo, Norway., Klaveness J; Department of Medicinal Chemistry, School of Pharmacy, University of Oslo, PO Box 1068 Blindern, N-0316 Oslo, Norway. Electronic address: jo.klaveness@farmasi.uio.no.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2014 Sep 15; Vol. 24 (18), pp. 4598-4602. Date of Electronic Publication: 2014 Jul 05.
DOI: 10.1016/j.bmcl.2014.06.083
Abstrakt: The synthesis and pharmacological data of some new and potent hydrophilic 5-HT4 receptor antagonists are described. Propanediol derivative 25 was identified as a potent antagonist with low affinity for the hERG potassium channel and promising pharmacokinetics.
(Copyright © 2014. Published by Elsevier Ltd.)
Databáze: MEDLINE
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