SAR development of a selective 5-HT1D antagonist/serotonin reuptake inhibitor lead using rapid parallel synthesis

Graham H Timms; John R Boot; Richard J Broadmore; Steven L Carney; Jane Cooper; Jeremy D Findlay; Jeremy Gilmore; Stephen Mitchell; Nick A Moore; Ian Pullar; Graham J Sanger; Rosemary Tomlinson; Beverly B Tree; Susan Wedley

doi:10.1016/j.bmcl.2004.03.003

SAR development of a selective 5-HT1D antagonist/serotonin reuptake inhibitor lead using rapid parallel synthesis

Bioorg Med Chem Lett. 2004 May 17;14(10):2469-72. doi: 10.1016/j.bmcl.2004.03.003.

Authors

Graham H Timms¹, John R Boot, Richard J Broadmore, Steven L Carney, Jane Cooper, Jeremy D Findlay, Jeremy Gilmore, Stephen Mitchell, Nick A Moore, Ian Pullar, Graham J Sanger, Rosemary Tomlinson, Beverly B Tree, Susan Wedley

Affiliation

¹ Eli Lilly and Co. Ltd, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK. timms_graham_h@lilly.com

PMID: 15109634
DOI: 10.1016/j.bmcl.2004.03.003

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.

MeSH terms

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
Selective Serotonin Reuptake Inhibitors / chemical synthesis*
Serotonin 5-HT1 Receptor Antagonists*
Serotonin Antagonists / chemical synthesis*
Structure-Activity Relationship

Substances

Heterocyclic Compounds, 4 or More Rings
Receptor, Serotonin, 5-HT1D
Serotonin 5-HT1 Receptor Antagonists
Serotonin Antagonists
Serotonin Uptake Inhibitors
Guanosine 5'-O-(3-Thiotriphosphate)