title: Novel, highly potent, selective 5-HT2A/D2 receptor antagonists as potential atypical antipsychotics.
abstract: The discovery of N-substituted-pyridoindolines and their binding affinities at the 5-HT(2A), 5-HT(2C) and D(2) receptors, and in vivo efficacy as 5-HT(2A) antagonists is described. The structure-activity relationship of a series of core tetracyclic derivatives with varying butyrophenone sidechains is also discussed. This study has led to the identification of potent, orally bioavailable 5-HT(2A)/D(2) receptor dual antagonists as potential atypical antipsychotics.
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Company, Wilmington, DE 19880, USA. taekyu.lee@bms.com
authors.forename: Taekyu
authors.initials: T
authors.lastname: Lee
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Robichaud
authors.forename: Kristopher E
authors.initials: KE
authors.lastname: Boyle
authors.forename: Yimin
authors.initials: Y
authors.lastname: Lu
authors.forename: David W
authors.initials: DW
authors.lastname: Robertson
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Miller
authors.forename: Larry W
authors.initials: LW
authors.lastname: Fitzgerald
authors.forename: John F
authors.initials: JF
authors.lastname: McElroy
authors.forename: Brian L
authors.initials: BL
authors.lastname: Largent
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004353:Drug Evaluation, Preclinical; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry*; D044405:Receptor, Serotonin, 5-HT2C / Q000737:chemistry*; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D006576:Heterocyclic Compounds, 4 or More Rings; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C