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Novel 2-methoxyacylhydrazones as potent, selective PDE10A inhibitors with activity in animal models of schizophrenia.

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.
AuthorsNeil S Cutshall, Rene Onrust, Alex Rohde, Sasha Gragerov, Lauren Hamilton, Kevin Harbol, Hui-Rong Shen, Shawn McKee, Charles Zuta, Galina Gragerova, Vince Florio, Thomas N Wheeler, Jennifer L Gage
JournalBioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 17 Pg. 5595-9 (Sep 01 2012) ISSN: 1464-3405 [Electronic] England
PMID22841436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Ltd. All rights reserved.
Chemical References
  • Antipsychotic Agents
  • Hydrazones
  • Phosphodiesterase Inhibitors
  • Pde10a protein, mouse
  • Phosphoric Diester Hydrolases
Topics
  • Animals
  • Antipsychotic Agents (chemistry, pharmacokinetics, therapeutic use)
  • Hydrazones (chemistry, pharmacokinetics, therapeutic use)
  • Mice
  • Phosphodiesterase Inhibitors (chemistry, pharmacokinetics, therapeutic use)
  • Phosphoric Diester Hydrolases (metabolism)
  • Schizophrenia (drug therapy, enzymology)
  • Structure-Activity Relationship

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