SAR development of a selective 5-HT1D antagonist/serotonin reuptake inhibitor lead using rapid parallel synthesis.
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.
Timms
Graham H
GH
Eli Lilly and Co. Ltd, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK. timms_graham_h@lilly.com
Boot
John R
JR
Broadmore
Richard J
RJ
Carney
Steven L
SL
Cooper
Jane
J
Findlay
Jeremy D
JD
Gilmore
Jeremy
J
Mitchell
Stephen
S
Moore
Nick A
NA
Pullar
Ian
I
Sanger
Graham J
GJ
Tomlinson
Rosemary
R
Tree
Beverly B
BB
Wedley
Susan
S
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
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