3-(5-chloro-2-oxobenzo[d]oxazol-3(2H)-yl) propanoic acid derivatives as kmo inhibitors

a technology of oxazol and derivatives, applied in the field of new drugs, can solve the problems of rapid progression to multiple organ dysfunction (mod), and no effective treatment availabl
US20160318884A1Inactive Publication Date: 2016-11-03GLAXOSMITHKLINE INTPROP DEV LTD
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Patent Information

Authority / Receiving Office
US · United States
Current Assignee / Owner
GLAXOSMITHKLINE INTPROP DEV LTD
Publication Date
2016-11-03
Estimated Expiration
Not applicable · inactive patent

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Abstract

A compound of formula (I) or a salt thereof are provided:wherein R1, X and R3 are defined in the specification, useful in the treatment of disorders mediated by KMO such as acute pancreatitis, chronic kidney disease, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure.
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Description

FIELD OF THE INVENTION

[0001] The present invention relates to novel 5-chlorobenzo[d]oxazol-2(3H)-one derivatives having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.BACKGROUND OF THE INVENTION

[0002] Kynurenine monooxygenase (KMO) is a flavin adenine dinucleotide (FAD) dependent monooxygenase located on the outer mitochondrial membrane. KMO is known to oxidise L-Kynurenine (KYN) to 3-hydroxykynurenine (3HK) as part of the major route of catabolism of tryptophan. 3HK is then converted to 3-hydroxyanthranilic acid and quinolinic acid by kynureninase (KYNU) and 3-hydroxyanthranilate 3,4-dioxygenase (3-HAAO).

[0003] KMO is highly expressed in tissues including the liver, placenta, kidney [Alberati-Giani, FEBS Lett. 410:407-412(1997)] endothelial cells and monocytes and at a lower level in microglia and macrophages in the brain.

[0004] Increased levels of 3HK and quinolinic acid and red...

Claims

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