US 12,459,906 B2
3-(5-chloro-2-oxobenzo[d]oxazol-3(2H)-yl) propanoic acid derivatives as KMO inhibitors
Anne Marie Jeanne Bouillot, Les Ulis (FR); Olivier Mirguet, Les Ulis (FR); John Liddle, Stevenage (GB); and Anne Louise Walker, Stevenage (GB)
Assigned to DR. FALK PHARMA GMBH, Freiburg (DE)
Filed by DR. FALK PHARMA GMBH, Freiburg (DE)
Filed on Jun. 2, 2022, as Appl. No. 17/830,532.
Application 17/830,532 is a continuation of application No. 16/521,283, filed on Jul. 24, 2019, granted, now 11,352,334.
Application 16/521,283 is a continuation of application No. 15/104,821, abandoned, previously published as PCT/EP2014/078221, filed on Dec. 17, 2014.
Claims priority of application No. 1322512 (GB), filed on Dec. 19, 2013.
Prior Publication US 2022/0298125 A1, Sep. 22, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 263/58 (2006.01); C07C 211/13 (2006.01); C07C 211/27 (2006.01); C07C 215/10 (2006.01); C07C 223/02 (2006.01); C07C 229/26 (2006.01); C07C 279/14 (2006.01); C07C 309/30 (2006.01); C07D 413/12 (2006.01)
CPC C07D 263/58 (2013.01) [C07C 211/13 (2013.01); C07C 211/27 (2013.01); C07C 215/10 (2013.01); C07C 223/02 (2013.01); C07C 229/26 (2013.01); C07C 279/14 (2013.01); C07C 309/30 (2013.01); C07D 413/12 (2013.01)] 18 Claims
 
1. A method of inhibiting KMO activity comprising administering an effective amount of a compound of Formula (I):

OG Complex Work Unit Chemistry
wherein:
X is a bond and Rt is H, -halo or CN;
X is CH2 and Rt is —H or —C1-3alkyl;
X is —O— and R1 is —C1-4alkyl, —(CH2)mCF3, —CHR2CH2OMe, —(CH2)nC3-4cycloalkyl, —(CH2)noxetane, -benzyl or —CHR2heteroaryl;
wherein:
the heteroaryl as defined in —CHR2 heteroaryl is additionally substituted by halo, methyl, ethyl or O;
m=1 or 2;
n=0 or 1;
R2=—H, -methyl or -ethyl;
R3=H or -methyl; or
a pharmaceutically acceptable salt thereof;
to a subject in need thereof, wherein diseases treatable by such inhibition include acute pancreatitis, Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, amyotrophic 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.