title: Inhibitors of the kynurenine pathway as neurotherapeutics: a patent review (2012-2015).
abstract: BACKGROUND
  The proven pathological alterations in the kynurenine pathway of tryptophan metabolism, either in preclinical models of neurological and psychiatric disorders or in human samples themselves, elicited numerous attempts to restore the altered balance via pharmaceutical manipulation of the pathway.
  
  
  METHODS
  The aim of the authors was to conduct a review of relevant scientific data on enzyme inhibitors of the kynurenine pathway, with special attention to pipeline drug development strategies based on relevant patent literature, covering the period of 2012-2015. Considering the magnitude of the topic, only the most prominent examples of lead compounds and substances necessary to enlighten structure activity relationships were reported.
  
  
  CONCLUSIONS
  Although the clinical and preclinical data are reassuring, there is a lack of applicable drugs in daily clinical practice. However, the recent determination of enzyme structures considerably promoted the development of potent inhibitors, most of them having been designed as a structural analog of the natural enzyme substrate. Especially, the inhibition of indolamine 2,3-dioxygenase in central nervous system tumors, the inhibition of kynurenine aminotransferase in cognitive dysfunction, and the inhibition of kynurenine 3-monooxygenase in neurodegenerative disorders, such as Huntington's disease, each show great promise.
authors.affiliation: a Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center , University of Szeged , Szeged , Hungary.
authors.forename: Dénes
authors.initials: D
authors.lastname: Zádori
authors.affiliation: a Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center , University of Szeged , Szeged , Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Veres
authors.affiliation: a Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center , University of Szeged , Szeged , Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Szalárdy
authors.affiliation: a Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center , University of Szeged , Szeged , Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Klivényi
authors.affiliation: b Institute of Pharmaceutical Chemistry and MTA-SZTE Stereochemistry Research Group, Faculty of Pharmacy , University of Szeged and Hungarian Academy of Sciences , Szeged , Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fülöp
authors.affiliation: c Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics , University of Szeged , Szeged , Hungary.|d MTA-SZTE Neuroscience Research Group, University of Szeged and Hungarian Academy of Sciences , Szeged , Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Toldi
authors.affiliation: a Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center , University of Szeged , Szeged , Hungary.|d MTA-SZTE Neuroscience Research Group, University of Szeged and Hungarian Academy of Sciences , Szeged , Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
mesh_terms: D000818:Animals; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy / Q000503:physiopathology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007737:Kynurenine / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000503:physiopathology; D010330:Patents as Topic; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007737:Kynurenine; D014364:Tryptophan
keywords: Inhibitors; kynurenine pathway; neurotherapeutics; tryptophan metabolism