title: N-Acylhydrazones as inhibitors of PDE10A.
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.
authors.affiliation: Omeros Corp., 1420 Fifth Ave., Suite 2600, Seattle, WA 98101, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gage
authors.forename: Rene
authors.initials: R
authors.lastname: Onrust
authors.forename: Derek
authors.initials: D
authors.lastname: Johnston
authors.forename: Andrew
authors.initials: A
authors.lastname: Osnowski
authors.forename: Wendy
authors.initials: W
authors.lastname: Macdonald
authors.forename: Lee
authors.initials: L
authors.lastname: Mitchell
authors.forename: László
authors.initials: L
authors.lastname: Urögdi
authors.forename: Alex
authors.initials: A
authors.lastname: Rohde
authors.forename: Kevin
authors.initials: K
authors.lastname: Harbol
authors.forename: Sasha
authors.initials: S
authors.lastname: Gragerov
authors.forename: György
authors.initials: G
authors.lastname: Dormán
authors.forename: Tom
authors.initials: T
authors.lastname: Wheeler
authors.forename: Vince
authors.initials: V
authors.lastname: Florio
authors.forename: Neil S
authors.initials: NS
authors.lastname: Cutshall
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D006835:Hydrazones / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D012559:Schizophrenia / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D006835:Hydrazones; D010726:Phosphodiesterase Inhibitors; D011804:Quinolines; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases