Synthesis and structure activity relationship of novel azaurazil and pyridopyramidine derivatives of arylpiperazine as potential and selective 5-Ht1a receptor agonists

MEDI 286

Vattoly J Majo1, Jaya Prabhakaran1, Lyudmila Savenkova1, J. John Mann2, and J. S. Dileep Kumar, dk2038@columbia.edu2. (1) Department of Psychiatry, Columbia University, 1051 Riverside Drive, Box:42, New York, NY 10032, (2) Department of Psychiatry and Division of Neuroscience, Columbia University and New York State Psychiatric Institute, 1051 Riverside Drive, Box:42, New York, NY 10032
The serotonin 5-HT1A receptor is implicated in the pathophysiology of major neuropsychiatric disorders including depression, suicidal behavior, panic disorder, epilepsy, bulimia, schizophrenia, Parkinson's disease, and Alzheimer's disease and is therefore an important target for drug therapy. 5-HT1A receptor agonists are being evaluated as antipsychotic drugs (APDs) with fewer side effects. We have recently found [11C-O-methyl]-2-{4-[4-(7-methoxynaphthalen-1-yl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione ([11C]MPT) as a 5-HT1A receptor agonist in vivo radiotracer. However, the lack of favorable kinetics at later time points of this ligand prompted us to evaluate the affinity and agonist profile of a series of arylpiperazines tethered to azauracil and pyridopyrimidine derivatives. The design, synthesis, SAR and in vivo efficacies of selected compounds will be presented.

 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007