Acetyl-CoA carboxylase (ACC) inhibitors and their use in diabetes, obesity and metabolic syndrome

1. A compound of formula (I), or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof,

wherein

R 1 is hydrogen, alkyl, haloalkyl, or cycloalkyl;

L 1 is —CR x R y —, —C(O)—, —O—, or —S—; wherein each of R x and R y is independently selected from the group consisting of hydrogen, alkyl, hydroxyalkyl and haloalkyl; or R x and R y together with the carbon to which they are attached form a three to six-membered monocyclic ring selected from the group consisting of cycloalkyl and heterocycle ring;

R A , R B and R C are each independently hydrogen, alkyl, halogen or haloalkyl;

Z is —CN, —OR 2 , -alkylenyl-OR 2 , —N(R 3 )(R 4 ) or -alkylenyl-N(R 3 )(R 4 );

R 2 , at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, —C(O)OR a , —S(O) 2 R a , —C(O)N(R a )(R b ), —S(O) 2 N(R a )(R b ), —C(O)R a , -alkylenyl-OR a , -alkylenyl-N(R a )(R b ), -alkylenyl-N(R b )C(O)OR a , -alkylenyl-N(R b )C(O)N(R a )(R b ), -alkylenyl-N(R b )C(O)R a , -alkylenyl-N(R b )S(O) 2 R a , -alkylenyl-C(O)OR a , -alkylenyl-S(O) 2 R a , -alkylenyl-S(O) 2 OR a , -alkylenyl-S(O) 2 N(R a )(R b ), -alkylenyl-C(O)N(R a )(R b ) and -alkylenyl-C(O)R a ;

R 3 , at each occurrence, is independently selected from the group consisting of hydrogen, alkyl and haloalkyl;

R 4 , at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, hydroxy, alkoxy, —C(═NH)NH 2 , —C(O)OR a , —S(O) 2 R a , —C(O)N(R a )(R b ), S(O) 2 N(R a )(R b ), —C(O)R a , —C(O)CH 2 C(O)R a , haloalkyl, -alkylenyl-OR a , -alkylenyl-N(R a )(R b ), -alkylenyl-N(R b )C(O)OR a , -alkylenyl-N(R b )C(O)N(R a )(R b ), -alkylenyl-N(R b )S(O) 2 R a , -alkylenyl-N(R b )C(O)R a , -alkylenyl-C(O)OR a , -alkylenyl-S(O) 2 R a , -alkylenyl-S(O) 2 OR a , -alkylenyl-S(O) 2 N(R a )(R b ), -alkylenyl-C(O)N(R a )(R b ) and -alkylenyl-C(O)R a ,

Ar 1 is phenyl or monocyclic heteroaryl, each of which is optionally fused to a phenyl or a monocyclic, five- or six-membered ring selected from the group consisting of cycloalkyl, cycloalkenyl, heterocycle and heteroaryl, and each Ar 1 is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of alkyl, alkenyl, —CN, —NO 2 , halogen, —OR 6 , —O—N═CH(R 5 ), —OC(O)R 5 , —OC(O)N(R 7 )(R 6 ), —OC(O)OR 5 , —OS(O) 2 R 5 , —SR 6 , —S(O)R 5 , —S(O) 2 R 5 , —S(O) 2 OR 6 , —S(O) 2 N(R 7 )(R 6 ), —C(O)R 6 , —C(O)N(R 7 )(R 6 ), —C(O)OR 6 , —C(O)N(R 7 )(R 6 ), —N(R 7 )(R 6 ), —N(H)—N═CH(R 5 ), —N(R)C(O)R 6 , —N(R)C(O)OR 6 , —N(R)S(O) 2 R 6 , —N(R)C(O)N(R 7 )(R 6 ), —N(R)S(O) 2 N(R 7 )(R 6 ), —R 8 , haloalkyl, cyanoalkyl, nitroalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylenyl-OC(O)R 5 , -alkylenyl-OC(O)N(R 7 )(R 6 ), -alkylenyl-OC(O)OR 5 , -alkylenyl-OS(O) 2 R 5 , -alkylenyl-SR 6 , -alkylenyl-S(O)R 5 , -alkylenyl-S(O) 2 R 5 , -alkylenyl-S(O) 2 OR 6 , -alkylenyl-S(O) 2 N(R 7 )(R 6 ), -alkylenyl-C(O)R 6 , -alkylenyl-C(O)N(R 7 )(R 6 ), -alkylenyl-C(O)OR 6 , -alkylenyl-C(O)N(R 7 )(R 6 ), -alkylenyl-N(R 7 )(R 6 ), -alkylenyl-N(R 7 )C(O)R 5 , -alkylenyl-N(R 7 )C(O)OR 5 , -alkylenyl-N(R 7 )S(O) 2 R 5 , -alkylenyl-N(R)C(O)N(R 7 )(R 6 ), -alkylenyl-N(R 7 )S(O) 2 N(R 7 )(R 6 ), and -alkylenyl-R 8 ;

R 5 , at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, —R 8 , and -alkylenyl-R 8 ;

R 6 , at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, —R 8 , and -alkylenyl-R 8 ;

R 7 , at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, arylalkyl, haloalkyl, and heteroarylalkyl;

R 8 , at each occurrence, is independently selected from the group consisting of aryl, heteroaryl, heterocycle, cycloalkyl and cycloalkenyl;

the cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, aryl moiety of the arylalkyl, and the heteroaryl moiety of the heteroarylalkyl represented by R 7 and R 8 , are each independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of alkyl, alkenyl, —CN, —NO 2 , halogen, ethylenedioxy, methylenedioxy, oxo, —OR a , —OC(O)R a , —OC(O)OR a , —OS(O) 2 R a , —S(alkyl), —S(O)alkyl, —S(O) 2 alkyl, —S(O) 2 OR a , —S(O) 2 NR a R b , —C(O)R a , —C(O)NR a R b , —C(O)OR a , —C(O)NR a R b , —NR a R b , —NOR a , —N(R b )C(O)R a , —N(R b )C(O)OR a , —N(R b )S(O) 2 R a , —N(R b )C(O)NR a R b , —N(R b )S(O) 2 NR a R b , haloalkyl, cyanoalkyl, nitroalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylenyl-OC(O)R a , -alkylenyl-OC(O)OR a , -alkylenyl-OS(O) 2 alkyl, -alkylenyl-S(alkyl), -alkylenyl-S(O)alkyl, -alkylenyl-S(O) 2 alkyl, -alkylenyl-S(O) 2 OR a , -alkylenyl-S(O) 2 NR a R b , -alkylenyl-C(O)R a , -alkylenyl-C(O)NR a R b , -alkylenyl-C(O)OR a , -alkylenyl-C(O)NR a R b , -alkylenyl-NR a R b , -alkylenyl-N(R b )C(O)OR a , -alkylenyl-N(R b )C(O)OR a , -alkylenyl-N(R b )S(O) 2 R a , -alkylenyl-N(R b )C(O)NR a R b , and -alkylenyl-N(R b )S(O) 2 NR a R b ;

R a at each occurrence is independently selected from the group consisting of hydrogen, alkyl, alkenyl and haloalkyl, and

R b at each occurrence is independently selected from the group consisting of hydrogen and alkyl.

2. The compound of claim 1 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is unsubstituted phenyl or unsubstituted pyridinyl, each of which is fused to an unsubstituted phenyl or unsubstituted pyridinyl; or Ar 1 is a group of formula (a), (b), (c) or (d)

A 1 , A 2 , A 3 and A 4 are —C(R E )—, or one or two of A 1 , A 2 , A 3 and A 4 is N and the others are —C(R E )—,

A 5 , A 6 , and A 7 are —C(R F )—, or one or two of A 5 , A 6 , and A 7 is N and the others are —C(R F )—,

A 8 , A 9 , and A 10 are —C(R F )—, or one or two of A 8 , A 9 , and A 10 is N and the others are —C(R F )—, wherein R E and R F , at each occurrence, are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, CN, NO 2 , halogen, hydroxy, alkoxy, —NH 2 —N(H)alkyl, —N(alkyl) 2 -SH, —S(alkyl), —S(O) 2 alkyl, —S(O) 2 Oalkyl, —C(O)OH, —C(O)Oalkyl, —C(O)H, haloalkyl, cyanoalkyl, nitroalkyl, hydroxyalkyl, alkoxyalkyl and haloalkoxyalkyl;

X is —OR 6 or —N(R 7 )(R 6 ); and

L 1 is —O—.

3. The compound of claim 1 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is unsubstituted phenyl or unsubstituted pyridinyl, each of which is fused to an unsubstituted phenyl or unsubstituted pyridinyl; or Ar 1 is a group of formula (a), (b), (c) or (d)

A 1 , A 2 , A 3 and A 4 are —C(R E )—,

A 5 , A 6 , and A 7 are —C(R F )—,

A 8 , A 9 , and A 10 are —C(R F )—, wherein R E and R F , at each occurrence, are each independently selected from the group consisting of hydrogen, —I, —Br, —Cl, and —F;

R A , R B and R C are hydrogen;

L 1 is —O—

X is —OR 6 wherein R 6 is selected from the group consisting of C 1 -C 6 alkyl and aryl, or X is —N(R 7 )(R 6 ) wherein R 7 is hydrogen and R 6 is aryl;

R 1 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —C 1 -C 6 alkylenyl-N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)R a wherein R a , is C 1 -C 6 alkyl;

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)R a wherein R a is C 1 -C 6 alkyl, or R 4 is —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or C 1 -C 6 alkyl.

4. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is formula (a),

A 1 , A 2 , A 3 and A 4 are —C(R E )—, or one of A 1 , A 2 , A 3 and A 4 is N and the others are —C(R E )—;

X is —OR 6 wherein R 6 is selected from the group consisting of C 1 -C 6 alkyl and aryl;

L 1 is —O—;

R 1 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —C 1 -C 6 alkylenyl-N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)R a wherein R a is C 1 -C 6 alkyl;

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)R a wherein R a is C 1 -C 6 alkyl, or R 4 is —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or C 1 -C 6 alkyl.

5. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is formula (a),

A 1 , A 2 , A 3 and A 4 are —C(R E )—, or one of A 1 , A 2 , A 3 and A 4 is N and the others are —C(R E )—; wherein each R E is independently selected from the group consisting of hydrogen, —I, —Br, —Cl, and —F;

R A , R B and R C are hydrogen;

X is —OR 6 wherein R 6 is selected from the group consisting of methyl, isopropyl, phenyl, and naphthyl, wherein phenyl and naphthyl are independently unsubstituted or substituted with one isopropoxy;

L 1 is —O—;

R 1 is methyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —CH 2 —N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)(methyl);

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)(methyl), or —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or methyl.

6. The compound of claim 5 selected from the group consisting of:

1-[2-(4-phenoxyphenoxy)-1,3-benzothiazol-6-yl]ethanol;

N-{1-[2-(4-phenoxyphenoxy)-1,3-benzothiazol-6-yl]ethyl}acetamide;

1-[2-(4-phenoxyphenoxy)-1,3-benzothiazol-6-yl]ethyl acetate;

1-[2-(4-phenoxyphenoxy)-1,3-benzothiazol-6-yl]ethanamine;

2-[2-(4-phenoxyphenoxy)-1,3-benzothiazol-6-yl]propanenitrile;

2-[2-(4-phenoxyphenoxy)-1,3-benzothiazol-6-yl]propan-1-amine;

N-{1-[2-(4-phenoxyphenoxy)-1,3-benzothiazol-6-yl]ethyl}urea;

N-{2-[2-(4-phenoxyphenoxy)-1,3-benzothiazol-6-yl]propyl}acetamide;

2-[2-(4-isopropoxyphenoxy)-1,3-benzothiazol-6-yl]propanenitrile;

2-[2-(4-isopropoxyphenoxy)-1,3-benzothiazol-6-yl]propan-1-amine;

N-{2-[2-(4-isopropoxyphenoxy)-1,3-benzothiazol-6-yl]propyl}acetamide; and

N-(2-{2-[4-(4-isopropoxyphenoxy)phenoxy]-1,3-benzothiazol-6-yl}propyl)acetamide or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof.

7. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is formula (a),

A 1 , A 2 , A 3 and A 4 are —C(R E )—, or one of A 1 , A 2 , A 3 and A 4 is N and the others are —C(R E )—;

X is —N(R 6 )(R 7 ) wherein R 7 is hydrogen and R 6 is aryl;

L 1 is —O—;

R 1 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —C 1 -C 6 alkylenyl-N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)R a wherein R a , is C 1 -C 6 alkyl;

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)R a wherein R a is C 1 -C 6 alkyl, or —C(O)N(R)(R b ) wherein R a is hydrogen and R b is hydrogen or C 1 -C 6 alkyl.

8. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is formula (a),

A 1 , A 2 , A 3 and A 4 are —C(R E )—, or one of A 1 , A 2 , A 3 and A 4 is N and the others are —C(R E )—;

wherein each R E is independently selected from the group consisting of hydrogen, —I, —Br, —Cl, and —F;

X is —N(R 6 )(R 7 ) wherein R 7 is hydrogen and R 6 is phenyl or naphthyl wherein each R 6 is independently unsubstituted or substituted with one isopropoxy;

R A , R B and R C are hydrogen;

L 1 is —O—;

R 1 is methyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —CH 2 —N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)(methyl);

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)(methyl), or —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or methyl.

9. The compound of claim 8 selected from the group consisting of:

N-{2-[2-(4-anilinophenoxy)-1,3-benzothiazol-6-yl]propyl}acetamide; and

N-(2-{2-[4-(2-naphthylamino)phenoxy]-1,3-benzothiazol-6-yl}propyl)acetamide

or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof.

10. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is formula (b),

A 1 , A 2 , A 3 and A 4 are —C(R E )—, or one of A 1 , A 2 , A 3 and A 4 is N and the others are —C(R E )—;

X is —OR 6 wherein R 6 is selected from the group consisting of C 1 -C 6 alkyl and aryl;

L 1 is —O—;

R 1 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —C 1 -C 6 alkylenyl-N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)R a wherein R a , is C 1 -C 6 alkyl;

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)R a wherein R a is C 1 -C 6 alkyl, or R 4 is —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or C 1 -C 6 alkyl.

11. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is formula (b),

A 1 , A 2 , A 3 and A 4 are —C(R E )—, or one of A 1 , A 2 , A 3 and A 4 is N and the others are —C(R E )—; wherein each R E is independently selected from the group consisting of hydrogen, —I, —Br, —Cl, and —F;

R A , R B and R C are hydrogen;

X is —OR 6 wherein R 6 is selected from the group consisting of methyl, isopropyl, phenyl and naphthyl, wherein the phenyl and the naphthyl are independently unsubstituted or substituted with one isopropoxy;

L 1 is —O—;

R 1 is methyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —CH 2 —N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)(methyl);

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)(methyl), or —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or methyl.

12. The compound of claim 11 selected from the group consisting of:

N-{2-[2-(3-phenoxyphenoxy)-1,3-benzothiazol-6-yl]propyl}acetamide; and

N-{2-[2-(3-isopropoxyphenoxy)-1,3-benzothiazol-6-yl]propyl}acetamide;

or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof.

13. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is formula (b),

A 1 , A 2 , A 3 and A 4 are —C(R E )—, or one of A 1 , A 2 , A 3 and A 4 is N and the others are —C(R E )—;

X is —N(R 6 )(R 7 ) wherein R 7 is hydrogen and R 6 is aryl;

L 1 is —O—;

R 1 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —C 1 -C 6 alkylenyl-N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)R a wherein R a , is C 1 -C 6 alkyl;

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)R a wherein R a is C 1 -C 6 alkyl, or R 4 is —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or C 1 -C 6 alkyl.

14. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is formula (b),

A 1 , A 2 , A 3 and A 4 are —C(R E )—, or one of A 1 , A 2 , A 3 and A 4 is N and the others are —C(R E )—; wherein each R E is independently selected from the group consisting of hydrogen, —I, —Br, —Cl, and —F;

R A , R B and R C are hydrogen;

X is —N(R 6 )(R 7 ) wherein R 7 is hydrogen and R 6 is phenyl or naphthyl, wherein each R 6 is independently unsubstituted or substituted with one isopropoxy;

L 1 is —O—;

R 1 is methyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —CH 2 —N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)(methyl);

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)(methyl), or —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or methyl.

15. The compound of claim 14 is N-{2-[2-(3-anilinophenoxy)-1,3-benzothiazol-6-yl]propyl}acetamide or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof.

16. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is formula (c) or (d),

A 5 , A 6 , and A 7 are —C(R F )—, or one of A 5 , A 6 , and A 7 is N and the others are —C(R F )—,

A 8 , A 9 , and A 10 are —C(R F )—, or one of A 8 , A 9 , and A 10 is N and the others are —C(R F )—;

X is OR 6 wherein R 6 is C 1 -C 6 alkyl or aryl, or —N(R 6 )(R 7 ) wherein R 7 is hydrogen and R 6 is aryl;

L 1 is —O—;

R 1 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —C 1 -C 6 alkylenyl-N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)R a wherein R a is C 1 -C 6 alkyl;

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)R a wherein R a is C 1 -C 6 alkyl, or R 4 is —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or C 1 -C 6 alkyl.

17. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is formula (c) or (d),

A 5 , A 6 , and A 7 are —C(R F )—, or one of A 5 , A 6 , and A 7 is N and the others are —C(R F )—,

A 8 , A 9 , and A 10 are —C(R F )—, or one of A 8 , A 9 , and A 10 is N and the others are —C(R F )—,

R F , at each occurrence, are each independently selected from the group consisting of hydrogen, —I, —Br, —Cl and —F;

R A , R B and R C are hydrogen;

X is OR 6 wherein R 6 is selected from the group consisting of methyl, isopropyl, phenyl and naphthyl, wherein the phenyl and naphthyl are independently unsubstituted or substituted with one isopropoxy; or X is —N(R 6 )(R 7 ) wherein R 7 is hydrogen and R 6 is phenyl or naphthyl, wherein the phenyl and naphthyl are independently unsubstituted or substituted with one isopropoxy;

L 1 is —O—;

R 1 is methyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —CH 2 —N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)(methyl);

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)(methyl), or —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or methyl.

18. The compound of claim 17 selected from the group consisting of:

N-(2-{2-[(6-methoxy-2-naphthyl)oxy]-1,3-benzothiazol-6-yl}propyl)acetamide; and

N-(2-{2-[(7-methoxy-2-naphthyl)oxy]-1,3-benzothiazol-6-yl}propyl)acetamide; or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof.

19. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is unsubstituted phenyl or unsubstituted pyridinyl, each of which is fused to an unsubstituted phenyl or unsubstituted pyridinyl;

L 1 is —O—;

R 1 is C 1 -C 6 alkyl or C 1 -C 6 haloalkyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —C 1 -C 6 alkylenyl-N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)R a wherein R a , is C 1 -C 6 alkyl;

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)R a wherein R a is C 1 -C 6 alkyl, or R 4 is —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or C 1 -C 6 alkyl.

20. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein

Ar 1 is unsubstituted phenyl or unsubstituted pyridinyl, each of which is fused to an unsubstituted phenyl or unsubstituted pyridinyl;

L 1 is —O—;

R A , R B and R C are hydrogen;

R 1 is methyl; and

Z is —CN, —OR 2 , —N(R 3 )(R 4 ), or —CH 2 —N(R 3 )(R 4 ); wherein

R 2 is hydrogen or —C(O)(methyl);

R 3 is hydrogen; and

R 4 is hydrogen, —C(O)(methyl), or —C(O)N(R a )(R b ) wherein R a is hydrogen and R b is hydrogen or methyl.

21. The compound of claim 20 selected from the group consisting of:

N-{2-[2-(2-naphthyloxy)-1,3-benzothiazol-6-yl]propyl}acetamide;

N-{2-[2-(quinolin-3-yloxy)-1,3-benzothiazol-6-yl]propyl}acetamide; and

N-{2-[2-(quinolin-6-yloxy)-1,3-benzothiazol-6-yl]propyl}acetamide or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof.

22. A method of treating metabolic syndrome in a mammal comprising administering a therapeutically effective amount of a compound of claim 1 .

23. A method of treating type II diabetes in a mammal comprising administering a therapeutically effective amount of a compound of claim 1 .

24. A method of treating obesity in a mammal comprising administering a therapeutically effective amount of a compound of claim 1 .

25. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable carrier.