1.
Bioorg Med Chem Lett
; 22(17): 5595-9, 2012 Sep 01.
Article
in English
| MEDLINE
| ID: mdl-22841436
ABSTRACT
A series of 2-methoxyacylhydrazones were optimized to yield compounds with high affinity for PDE10A. Several compounds demonstrated efficacy in animal models of schizophrenia, including conditioned avoidance response and a pro-psychotic phencyclidine hyperactivity model.
Subject(s)
Hydrazones/chemistry , Hydrazones/therapeutic use , Phosphodiesterase Inhibitors/chemistry , Phosphodiesterase Inhibitors/therapeutic use , Phosphoric Diester Hydrolases/metabolism , Schizophrenia/drug therapy , Schizophrenia/enzymology , Animals , Antipsychotic Agents/chemistry , Antipsychotic Agents/pharmacokinetics , Antipsychotic Agents/therapeutic use , Hydrazones/pharmacokinetics , Mice , Phosphodiesterase Inhibitors/pharmacokinetics , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 21(14): 4155-9, 2011 Jul 15.
Article
in English
| MEDLINE
| ID: mdl-21696955
ABSTRACT
Cyclic nucleotide phosphodiesterases (PDEs) are represented by a large superfamily of enzymes. A series of hydrazone-based inhibitors was synthesized and shown to be novel, potent, and selective against PDE10A. Optimized compounds of this class were efficacious in animal models of schizophrenia and may be useful for the treatment of this disease.
