title: SAR development of a selective 5-HT1D antagonist/serotonin reuptake inhibitor lead using rapid parallel synthesis.
abstract: Incorporation of an SRI (serotonin reuptake inhibitor) pharmacophore into a selective 5-HT(1D) agonist has led to the discovery of a molecule having both 5-HT(1D) antagonist and SRI activity. RPS methodology was used to develop the SAR and identify potential approaches to reduce unwanted adrenergic alpha 1 and dopamine D(2) cross-reactivities.
authors.affiliation: Eli Lilly and Co. Ltd, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK. timms_graham_h@lilly.com
authors.forename: Graham H
authors.initials: GH
authors.lastname: Timms
authors.forename: John R
authors.initials: JR
authors.lastname: Boot
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Broadmore
authors.forename: Steven L
authors.initials: SL
authors.lastname: Carney
authors.forename: Jane
authors.initials: J
authors.lastname: Cooper
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Findlay
authors.forename: Jeremy
authors.initials: J
authors.lastname: Gilmore
authors.forename: Stephen
authors.initials: S
authors.lastname: Mitchell
authors.forename: Nick A
authors.initials: NA
authors.lastname: Moore
authors.forename: Ian
authors.initials: I
authors.lastname: Pullar
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Sanger
authors.forename: Rosemary
authors.initials: R
authors.lastname: Tomlinson
authors.forename: Beverly B
authors.initials: BB
authors.lastname: Tree
authors.forename: Susan
authors.initials: S
authors.lastname: Wedley
mesh_terms: D002460:Cell Line; D003429:Cross Reactions; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000138:chemical synthesis*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
chemical_list: D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006576:Heterocyclic Compounds, 4 or More Rings; D044346:Receptor, Serotonin, 5-HT1D; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors