Ligand conformation has a definitive effect on 5-HT1A and serotonin reuptake affinity

Kenneth M Boy; Michael Dee; Joseph Yevich; John Torrente; Qi Gao; Lawrence Iben; Arlene Stark; Ronald J Mattson

doi:10.1016/j.bmcl.2004.06.050

Ligand conformation has a definitive effect on 5-HT1A and serotonin reuptake affinity

Bioorg Med Chem Lett. 2004 Sep 6;14(17):4467-70. doi: 10.1016/j.bmcl.2004.06.050.

Authors

Kenneth M Boy¹, Michael Dee, Joseph Yevich, John Torrente, Qi Gao, Lawrence Iben, Arlene Stark, Ronald J Mattson

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. boyk@bms.com

PMID: 15357973
DOI: 10.1016/j.bmcl.2004.06.050

Abstract

Conformationally constrained aryl cyclohexanes and cyclohexenes based on aryl cyclohexanols 1 were prepared. Locking the aryl ring in plane with the cyclohexane moiety provided potent SSRIs 3. Conversely, fixing the aryl ring perpendicular to the cyclohexane ring via a spiro lactone provided balanced 5-HT1A antagonists with mid-nanomolar range SSRI potency (compounds 2).

MeSH terms

Ligands
Molecular Conformation
Receptor, Serotonin, 5-HT1A / metabolism*
Selective Serotonin Reuptake Inhibitors / chemistry*
Selective Serotonin Reuptake Inhibitors / metabolism*
Serotonin / metabolism*

Substances

Ligands
Serotonin Uptake Inhibitors
Receptor, Serotonin, 5-HT1A
Serotonin