Patented PDE10A inhibitors: novel compounds since 2007.
BACKGROUND
PDE10A inhibition has generated much excitement as a potential novel mechanism for the treatment of the positive symptoms of schizophrenia. PDE10A is only '10 years old' as a drug discovery target since it was first discovered in 1999, and thus PDE10A is an example of the modern drug discovery paradigm demonstrating the highly increased speed by which novel targets can be validated, hits identified, lead-optimization performed and compounds progressed into clinical trials. At least one PDE10A inhibitor compound has been progressed to clinical Phase II for the treatment of schizophrenia. And preclinical evidence suggests that a PDE10A inhibitor could provide antipsychotic, pro-cognitive and negative symptom efficacy in the same dose range.


METHODS
The review surveys advances in the medicinal chemistry of PDE10A through the patent literature since 2007. The article is supplemented with selected publications from the scientific literature.


RESULTS
Readers will gain an up to date overview of all patents published in the PDE10A field within the last 2 years and be able to judge about the structure-activity relationship and drugability of most progressed PDE10A compounds.


CONCLUSIONS
PDE10A inhibitors will possibly be involved in the treatment of schizophrenia. The field is rapidly approaching a clinical validation of PDE10A inhibitors.
Kehler
Jan
J
CNS Medicinal Chemistry, H. Lundbeck A/S, 813 building G1, Valby, Denmark. jke@lundbeck.com
Kilburn
John Paul
JP
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D010330:Patents as Topic; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D010726:Phosphodiesterase Inhibitors; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases