title: Discovery and pharmacological profile of new hydrophilic 5-HT(4) receptor antagonists.
abstract: 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.
authors.affiliation: 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.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Brudeli
authors.affiliation: 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.
authors.forename: Mirusha
authors.initials: M
authors.lastname: Navaratnarajah
authors.affiliation: 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.
authors.forename: Kjetil Wessel
authors.initials: KW
authors.lastname: Andressen
authors.affiliation: 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.
authors.forename: Ornella
authors.initials: O
authors.lastname: Manfra
authors.affiliation: 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.
authors.forename: Lise Román
authors.initials: LR
authors.lastname: Moltzau
authors.affiliation: Drug Discovery Laboratory AS, Oslo Innovation Center, N-0349 Oslo, Norway.
authors.forename: Nils Olav
authors.initials: NO
authors.lastname: Nilsen
authors.affiliation: 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.
authors.forename: Finn Olav
authors.initials: FO
authors.lastname: Levy
authors.affiliation: 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.
authors.forename: Jo
authors.initials: J
authors.lastname: Klaveness
mesh_terms: D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D011409:Propylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D058832:Serotonin 5-HT4 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D011409:Propylene Glycols; D058832:Serotonin 5-HT4 Receptor Antagonists; D044422:Receptors, Serotonin, 5-HT4
keywords: 5-HT(4) receptor antagonists; Pharmacokinetic; hERG