Small molecule inhibitors of kynurenine-3-monooxygenase

A compound of Formula Ia or Ib:

• wherein
• R1 is hydrogen or nitro and R2 is nitro;
• R3 is selected from the group consisting of hydrogen, substituted alkyl, alkoxy, substituted alkoxy, amino, substituted amino, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• R4 and R5 independently are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amino, substituted amino, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, cyano, halo, hydroxyl, acyl, nitro, mercapto, alkylthio, substituted alkylthio, substituted sulfonyl, substituted sulfonyloxy, substituted sulfinyl, and aminocarbonyl, or R4 and R5 join together to form a ring selected from the group consisting of C5-C7 cycloalkyl, substituted C5-C7 cycloalkyl, C5-C7 heterocycloalkyl, substituted C5-C7 heterocycloalkyl, heteroaryl, and substituted heteroaryl;
• and
• R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, carboxyl, carboxyl ester, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• or a tautomer and/or a pharmaceutically acceptable salt thereof with a proviso that only one of R3 or R6 can be hydrogen and with the further proviso that when R3 is hydrogen then R6 is not alkyl.

A compound of Formula Ia or Ib:

• wherein:
• R1 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, substituted alkoxy, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amino, substituted amino, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, cyano, halo, acyl, nitro, mercapto, alkylthio, substituted alkylthio, substituted sulfonyl, substituted sulfonyloxy, substituted sulfinyl, and aminocarbonyl;
• R2 is selected from the group consisting of alkyl, substituted alkyl, substituted alkoxy, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amino, substituted amino, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, cyano, halo, acyl, nitro, mercapto, alkylthio, substituted alkylthio, substituted sulfonyl, substituted sulfonyloxy, substituted sulfinyl, and aminocarbonyl;
• R3 is selected from the group consisting of alkyl substituted with 1 to 3 R30, alkoxy, substituted alkoxy, amino, substituted amino, heteroaryl, and substituted heteroaryl, wherein each R30 is independently selected from the group consisting of alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, aryloxy, substituted aryloxy, arylthio, substituted arylthio, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, cycloalkyl, substituted cycloalkyl, cycloalkyloxy, substituted cycloalkyloxy, cycloalkylthio, substituted cycloalkylthio, guanidino, substituted guanidino, halo, hydroxy, heteroaryl, substituted heteroaryl, heteroaryloxy, substituted heteroaryloxy, heteroarylthio, substituted heteroarylthio, heterocyclic, substituted heterocyclic, heterocyclyloxy, substituted heterocyclyloxy, heterocyclylthio, substituted heterocyclylthio, nitro, SO3H, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, and substituted alkylthio;
• R4 and R5 independently are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amino, substituted amino, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, cyano, halo, hydroxyl, acyl, nitro, mercapto, alkylthio, substituted alkylthio, substituted sulfonyl, substituted sulfonyloxy, substituted sulfinyl, and aminocarbonyl, or R4 and R5 join together to form a ring selected from the group consisting of C5-C7 cycloalkyl, substituted C5-C7 cycloalkyl, C5-C7 heterocycloalkyl, substituted C5-C7 heterocycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• and
• R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, carboxyl, carboxyl ester, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• or a tautomer and/or a pharmaceutically acceptable salt thereof.

A compound of Formula Ia or Ib:

• wherein
• R1 is hydrogen or nitro and R2 is nitro;
• R3 is selected from the group consisting of substituted alkyl, alkoxy, substituted alkoxy, amino, substituted amino, heteroaryl, and substituted heteroaryl;
• R4 and R5 independently are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amino, substituted amino, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, cyano, halo, hydroxyl, acyl, nitro, mercapto, alkylthio, substituted alkylthio, substituted sulfonyl, substituted sulfonyloxy, substituted sulfinyl, and aminocarbonyl, or R4 and R5 join together to form a ring selected from the group consisting of C5-C7 cycloalkyl, substituted C5-C7 cycloalkyl, C5-C7 heterocycloalkyl, substituted C5-C7 heterocycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• and
• R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, carboxyl, carboxyl ester, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• or a tautomer and/or a pharmaceutically acceptable salt thereof.