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SAR development of a selective 5-HT1D antagonist/serotonin reuptake inhibitor lead using rapid parallel synthesis.
Timms, Graham H; Boot, John R; Broadmore, Richard J; Carney, Steven L; Cooper, Jane; Findlay, Jeremy D; Gilmore, Jeremy; Mitchell, Stephen; Moore, Nick A; Pullar, Ian; Sanger, Graham J; Tomlinson, Rosemary; Tree, Beverly B; Wedley, Susan.
Bioorg Med Chem Lett ; 14(10): 2469-72, 2004 May 17.
Article in English | MEDLINE | ID: mdl-15109634

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.


Subject(s)
Selective Serotonin Reuptake Inhibitors/chemical synthesis , Serotonin 5-HT1 Receptor Antagonists , Serotonin Antagonists/chemical synthesis , Cell Line , Cross Reactions , Guanosine 5'-O-(3-Thiotriphosphate)/metabolism , Heterocyclic Compounds, 4 or More Rings/chemical synthesis , Heterocyclic Compounds, 4 or More Rings/pharmacology , Humans , Receptor, Serotonin, 5-HT1D/metabolism , Structure-Activity Relationship
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