749913-61-9Relevant articles and documents
Ligand conformation has a definitive effect on 5-HT1A and serotonin reuptake affinity
Boy, Kenneth M.,Dee, Michael,Yevich, Joseph,Torrente, John,Gao, Qi,Iben, Lawrence,Stark, Arlene,Mattson, Ronald J.
, p. 4467 - 4470 (2007/10/03)
Conformationally constrained cyclohexanes and cyclohexenes were prepared and tested for 5-HT1A and SSRI activity. The conformation of the dioxyaryl ring with respect to the cyclohexane ring is a key factor for selecting the relative potency of the compounds at the two receptors studied. 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).