[1,4]Diazepine[7,8,1-hi]indole derivatives as antipsychotic and antiobesity agents

MEDI 285

Hong Gao, gaoh1@wyeth.com1, Gary Stack, stackg@wyeth.com2, Boyd L. Harrison, harrisb3@wyeth.com1, Hossein Mazandarani3, Jean Zhang3, Sachin Kalgonkar3, Sharon Rosenzweig-Lipson3, John Dunlop3, Terry Andree3, and Lee Schechter3. (1) Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, (2) Medicinal Chemistry, Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, (3) Wyeth Neuroscience, CN 8000, Princeton, NJ 08543
5-HT2C agonists and partial agonists represent a novel therapeutic approach toward the treatment of schizophrenia. At present, the most widespread treatments for schizophrenia are the ‘atypical' antipsychotics, which combine dopamine (D2) receptor antagonism with serotonin (5-HT2A) receptor antagonism. Despite the reported advances in efficacy and side-effect liability of atypical antipsychotics over typical antipsychotics, these compounds do not adequately treat all of the symptoms of schizophrenia and are accompanied by problematic side effects including weight gain. Novel antipsychotics which are effective in treating the symptoms in schizophrenia without producing weight gain would represent a significant advance in the treatment of schizophrenia. A series of benzodiazocinoindoles (I) were investigated and several analogs found to be potent and selective 5-HT2C agonists and partial agonists with affinities in the 10 nM range. Herein we report the synthesis and SAR of these novel benzodiazocinoindoles.

 

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