The discovery and synthesis of JNJ 31020028, a small molecule antagonist of the Neuropeptide Y Y sub(2) receptor

A series of small molecules based on a chemotype identified from our compound collection were synthesized and tested for binding affinity (IC sub(50)) at the human Neuropeptide Y Y sub(2) receptor (NPY Y sub(2)). Six of the 23 analogs tested possessed an NPY Y sub(2) IC sub(50) [less-than-or-equals, slant] 15 nM. One member of this series, JNJ 31020028, is a selective, high affinity, receptor antagonist existing as a racemic mixture. As such a synthetic route to the desired enantiomer was designed starting from commercially available (S)-(+)-mandelic acid.