title: Design and synthesis of piperazinylpyrimidinones as novel selective 5-HT(2C) agonists.
abstract: This Letter reports the design and synthesis of several novel series of piperazinyl pyrimidinones as 5-HT(2C) agonists. Several of the compounds presented exhibit good in vitro potency and selectivity over the closely related 5-HT(2A) and 5-HT(2B) receptors. Compound 11 was active in in vivo models of stress urinary incontinence.
authors.affiliation: Department of Medicinal Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent CT13 9NJ, UK. mark.d.andrews@pfizer.com
authors.forename: Mark D
authors.initials: MD
authors.lastname: Andrews
authors.forename: Martin P
authors.initials: MP
authors.lastname: Green
authors.forename: Charlotte M N
authors.initials: CM
authors.lastname: Allerton
authors.forename: David V
authors.initials: DV
authors.lastname: Batchelor
authors.forename: Julian
authors.initials: J
authors.lastname: Blagg
authors.forename: Alan D
authors.initials: AD
authors.lastname: Brown
authors.forename: David W
authors.initials: DW
authors.lastname: Gordon
authors.forename: Gordon
authors.initials: G
authors.lastname: McMurray
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Millns
authors.forename: Carly L
authors.initials: CL
authors.lastname: Nichols
authors.forename: Lesa
authors.initials: L
authors.lastname: Watson
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D006801:Humans; D011744:Pyrimidinones / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D044403:Receptor, Serotonin, 5-HT2B / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014521:Urethra / Q000187:drug effects; D014549:Urinary Incontinence / Q000188:drug therapy
chemical_list: D011744:Pyrimidinones; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists