title: Synthesis and SAR of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones as 5-HT2C receptor agonists.
abstract: A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones is described, several examples of which exhibit potent 5-HT(2C) agonism with excellent selectivity over the closely related 5-HT(2A) and 5-HT(2B) receptors. Compounds such as 38 and 44 were shown to be effective in reducing food intake in an acute rat feeding model.
authors.affiliation: Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08543-5400, USA. john.fevig@bms.com
authors.forename: John M
authors.initials: JM
authors.lastname: Fevig
authors.forename: Jianxin
authors.initials: J
authors.lastname: Feng
authors.forename: Karen A
authors.initials: KA
authors.lastname: Rossi
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Miller
authors.forename: Ginger
authors.initials: G
authors.lastname: Wu
authors.forename: Chen-Pin
authors.initials: CP
authors.lastname: Hung
authors.forename: Thao
authors.initials: T
authors.lastname: Ung
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Malmstrom
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: William J
authors.initials: WJ
authors.lastname: Keim
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Cullen
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Rohrbach
authors.forename: Qinling
authors.initials: Q
authors.lastname: Qu
authors.forename: Jinping
authors.initials: J
authors.lastname: Gan
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Pelleymounter
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Robl
mesh_terms: D000818:Animals; D006207:Half-Life; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry / Q000378:metabolism; 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 / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D007546:Isoquinolines; D011758:Pyrroles; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists