title: Selective 5-HT2C receptor agonists: Design and synthesis of pyridazine-fused azepines.
abstract: Heterocycle-fused azepines are discussed as potent 5-HT2C receptor agonists with excellent selectivity over 5-HT2B agonism. Synthesis and structure activity relationships are outlined for a series of bicyclic pyridazino[3,4-d]azepines. By comparison with earlier published work, in vitro assays predict a high probability for achieving CNS penetration for a potent and selective compound 15a, a pre-requisite to achieve in vivo efficacy.
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent CT13 9NJ, UK.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Green
authors.affiliation: Discovery Biology, Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent CT13 9NJ, UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: McMurray
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent CT13 9NJ, UK. Electronic address: ian.storer@pfizer.com.
authors.forename: R Ian
authors.initials: RI
authors.lastname: Storer
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D004285:Dogs; D015195:Drug Design; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D011485:Protein Binding; D011724:Pyridazines / Q000737:chemistry*; D044403:Receptor, Serotonin, 5-HT2B / Q000737:chemistry / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000737:chemistry / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001381:Azepines; D011724:Pyridazines; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; C062482:pyridazine
keywords: 5-HT(2C) receptor agonists; CNS penetration; Obesity; Pyridazino[3,4-d]azepines; Urinary incontinence