title: Model studies on a synthetically facile series of N-substituted phenyl-N'-pyridin-3-yl ureas leading to 1-(3-pyridylcarbamoyl) indolines that are potent and selective 5-HT(2C/2B) receptor antagonists.
abstract: A model series of 5-HT2C antagonists have been prepared by rapid parallel synthesis. These N-substituted phenyl-N'-pyridin-3-yl ureas were found to have a range of 5-HT2C receptor affinities and selectivities over the closely related 5-HT2A receptor. Extrapolation of simple SAR, derived from this set of compounds, to the more active but synthetically more complex 1-(3-pyridylcarbamoyl)indoline series allowed us to target optimal substitution patterns and identify potent and selective 5-HT(2C/2B) antagonists.
authors.affiliation: SmithKline Beecham Pharmaceuticals Discovery Research, New Frontiers Science Park, Harlow, Essex, UK. steve_bromidge-1@sbphrd.com
authors.forename: S M
authors.initials: SM
authors.lastname: Bromidge
authors.forename: S
authors.initials: S
authors.lastname: Dabbs
authors.forename: D T
authors.initials: DT
authors.lastname: Davies
authors.forename: S
authors.initials: S
authors.lastname: Davies
authors.forename: D M
authors.initials: DM
authors.lastname: Duckworth
authors.forename: I T
authors.initials: IT
authors.lastname: Forbes
authors.forename: A
authors.initials: A
authors.lastname: Gadre
authors.forename: P
authors.initials: P
authors.lastname: Ham
authors.forename: G E
authors.initials: GE
authors.lastname: Jones
authors.forename: F D
authors.initials: FD
authors.lastname: King
authors.forename: D V
authors.initials: DV
authors.lastname: Saunders
authors.forename: K M
authors.initials: KM
authors.lastname: Thewlis
authors.forename: D
authors.initials: D
authors.lastname: Vyas
authors.forename: T P
authors.initials: TP
authors.lastname: Blackburn
authors.forename: V
authors.initials: V
authors.lastname: Holland
authors.forename: G A
authors.initials: GA
authors.lastname: Kennett
authors.forename: G J
authors.initials: GJ
authors.lastname: Riley
authors.forename: M D
authors.initials: MD
authors.lastname: Wood
mesh_terms: D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010671:Phenylurea Compounds; D011725:Pyridines; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists