Modulators of acetyl-coenzyme A carboxylase and methods of use thereof

A compound of formula I:

• wherein:
• R1 is hydrogen or alkyl, wherein the alkyl may be optionally substituted with halogen, hydroxyl, alkoxy, haloalkoxy, cyano, amino, alkylamino, dialkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, acyl, alkoxycarbonyl, aryl or heteroaryl,
• where aryl or heteroaryl may be further optionally substituted with one to three R2;
• Ar is aryl or heteroaryl, each of which may be optionally substituted from one to three times by:
• halogen, hydroxyl, alkyl, haloalkyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, cyano, amino, alkylamino, dialkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, acyl, alkoxycarbonyl, aryl or heteroaryl,
• where aryl or heteroaryl may be further optionally substituted with one to three R2;
• W and Y each independently are N or CH;
• Z is O;
• each R2 is independently halogen, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, alkylthio, alkylsulfinyl, alkylsulfonyl, acyl or alkoxycarbonyl;
• X1, X2, and X3 are each independently hydrogen, halogen, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, haloalkenyl, alkenyloxy, haloalkenyloxy, alkynyl, haloalkynyl, alkynyloxy, haloalkynyloxy, cyano, R5R6N—, alkylthio, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, carbamoylamino, acyl, acylamino, carboxy, alkoxycarbonyl, arylalkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, carboxyalkoxy, alkoxycarbonylalkoxy, alkylaminocarbonyloxy, dialkylaminocarbonyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl,
• where aryl, heteroaryl, arylalkyl, or heteroarylalkyl may be optionally substituted with one to three R4;
• or when W and Y are both CH, X1 and X2 taken together on adjacent carbon atoms form a 3- to 5-membered bridged ring consisting of elements from methylene, substituted methylene, —CH═, —C(R4)═, C═O, —N═, NH, O, or S(O)n;
• each R4 is independently halogen, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cyano, amino, alkylamino, dialkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, carbamoylamino, acyl, acylamino, carboxy, alkoxycarbonyl, arylalkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, or dialkylaminocarbonyloxy;
• each R5 and R6 are independently hydrogen, alkyl, arylalkyl, alkoxyalkyl, hydroxyalkyl;
• or taken together to form a 5- or 6-member heterocycle containing 2-5 C-atoms, 0-1 O-atom, 0-1 S-atom, and 1-3 N-atoms, which heterocycle may be optionally substituted on a C-atom or N-atom by alkyl, acyl, alkoxycarbonyl, or alkylsulfonyl;
• n is 0, 1, or 2;
• or a pharmaceutically or agriculturally acceptable salt thereof;
• subject to the proviso that
• when R1 is H, Z is O, W and Y are CH, X1 is H, and Ar is phenyl, then X2 and X3 cannot be taken together at the 7,8-positions of the benzoxazinone to form a fused phenyl ring;
• when R1 is H, Z is O, W and Y are CH, X1 and X2 and X3 are all H, then Ar cannot be 2-fluorophenyl, 4-aminocarbonyl-2-fluorophenyl, 4-amino-5-chloro-methoxyphenyl, 4-(3-thietanyloxy)phenyl, 3-pyridyl, 2-pyrazinyl, 2,3-dihydro-l-methylsulfonyl-1H-indol-5-yl, 2,3-dihydro-1-(2-methoxyethyl)-2-oxo-1H-benzimidazol-5-yl, 2,3-dihydro-1,3-dimethyl-2-oxo-1H-benzimidazol-5-yl, 3,4-dihydro-3-oxo-2H-1,4-benzoxazin-6-yl, 2,3-dihydro-2-(2-methylpropyl)-3-oxo-1H-isoindol-4-yl, or 4-(3,5-dimethylpyrazol-1-yl)phenyl;
• or
• when R1 is H, Z is O, W and Y are CH, and X1 and X2 and X3 are all H, or X1 is 6-bromo and X2 and X3 are H, then Ar cannot be 2-amino-1-benzothiophen-3-yl or 2-(3-ethylureido)-1-benzothiophen-3-yl.