Inhibitors of the kynurenine pathway as neurotherapeutics: a patent review (2012-2015).

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.