title: Studies towards the identification of a new generation of atypical antipsychotic agents.
abstract: A rational structure-activity relationship study around compound (1) is reported. The lead optimisation programme led to the identification of sulfonamide (25), a molecule combining dopamine D2/D3 receptor antagonism with serotonin 5-HT2A, 5-HT2C, 5-HT6 receptor antagonism for an effective treatment of schizophrenia. Compound (25) was shown to possess the required in vivo activity with no EPS liability.
authors.affiliation: Psychiatry Centre of Excellence for Drug Discovery, New Frontiers Science Park, Harlow, Essex CM19 5AW, UK. Vincenzo_2_garzya@gsk.com
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Garzya
authors.forename: Ian T
authors.initials: IT
authors.lastname: Forbes
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Gribble
authors.forename: Mike S
authors.initials: MS
authors.lastname: Hadley
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lightfoot
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Payne
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Smith
authors.forename: Sara E
authors.initials: SE
authors.lastname: Douglas
authors.forename: David G
authors.initials: DG
authors.lastname: Cooper
authors.forename: Ian G
authors.initials: IG
authors.lastname: Stansfield
authors.forename: Malcom
authors.initials: M
authors.lastname: Meeson
authors.forename: Emma E
authors.initials: EE
authors.lastname: Dodds
authors.forename: Declan N C
authors.initials: DN
authors.lastname: Jones
authors.forename: Martyn
authors.initials: M
authors.lastname: Wood
authors.forename: Charlie
authors.initials: C
authors.lastname: Reavill
authors.forename: Carol A
authors.initials: CA
authors.lastname: Scorer
authors.forename: Angela
authors.initials: A
authors.lastname: Worby
authors.forename: Graham
authors.initials: G
authors.lastname: Riley
authors.forename: Peter
authors.initials: P
authors.lastname: Eddershaw
authors.forename: Chris
authors.initials: C
authors.lastname: Ioannou
authors.forename: Daniele
authors.initials: D
authors.lastname: Donati
authors.forename: Jim J
authors.initials: JJ
authors.lastname: Hagan
authors.forename: Emiliangelo A
authors.initials: EA
authors.lastname: Ratti
mesh_terms: D000478:Alkylation; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D015195:Drug Design; D006801:Humans; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects; D011994:Recombinant Proteins / Q000187:drug effects; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D050637:Receptors, Dopamine D3; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; D013449:Sulfonamides; C097216:serotonin 6 receptor; D003577:Cytochrome P-450 Enzyme System