Heterocyclic modulators of lipid synthesis
Compounds that are fatty acid synthesis modulators are provided. The compounds may be used to treat disorders characterized by disregulation of the fatty acid synthase function by modulating the function and/or the fatty acid synthase pathway. Methods are provided for treating such disorders including viral infections, such as hepatitis C infection, cancer and metabolic disorders, such as non-alcoholic steatohepatitis (NASH).
1. A compound having Structure (VI-J):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is H, —CN, halogen, C 1 -C 4 straight or branched alkyl, —O—(C 3 -C 5 cycloalkyl), or —O—(C 1 -C 4 straight or branched alkyl), wherein:
the C 3 -C 5 cycloalkyl optionally includes an oxygen or nitrogen heteroatom; and when R 1 is not H, —CN or halogen, it is optionally substituted with one or more halogens;
each R 2 is independently H, halogen or C 1 -C 4 straight or branched alkyl;
R 3 is H, —OH, or halogen;
R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl;
R 22 is H, halogen, or C 1 -C 2 alkyl;
R 35 is —C(O)—R 351 , —C(O)—NHR 351 , —C(O)—O—R 351 or S(O) 2 R 351 ; and
R 351 is C 1 -C 6 straight or branched alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein alkyl is optionally substituted with one or two substituents selected from cycloalkyl, heterocycle, aryl, and heteroaryl.
2. The compound of claim 1 , wherein R 3 is H or halogen.
3. The compound of claim 2 , wherein R 21 is cyclobutyl.
4. The compound of claim 3 , wherein R 1 is —CN.
5. The compound of claim 4 , wherein R 22 is H.
6. The compound of claim 5 , wherein R 35 is —C(O)—NH—R 351 .
7. The compound of claim 6 , wherein R 351 is (R)-3-tetrahydrofuranyl, (S)-3-tetrahydrofuranyl, (R)-(tetrahydrofuran-2-yl)methyl or (S)-(tetrahydrofuran-2-yl)methyl.
8. The compound of claim 5 , wherein R 35 is —C(O)—O—R 351 .
9. The compound of claim 8 , wherein R 351 is (R)-3-tetrahydrofuranyl or (S)-3-tetrahydrofuranyl.
10. The compound of claim 1 , having a formula selected from the group consisting of:
11. The compound of claim 6 , wherein R 351 is C 1 -C 6 straight or branched alkyl optionally substituted with one or two substituents selected from cycloalkyl, heterocycle, aryl, and heteroaryl.
12. The compound of claim 6 , wherein R 351 is (R)-(tetrahydrofuran-2-yl)methyl or (S) (tetrahydrofuran-2-yl)methyl.
13. The compound of claim 6 , wherein is R 351 is cycloalkyl, heterocyclyl, aryl or heteroaryl.
14. The compound of claim 1 , wherein R 35 is —C(O)—NH—R 351 .
15. The compound of claim 14 , wherein R 351 is C 1 -C 6 straight or branched alkyl optionally substituted with one or two substituents selected from cycloalkyl, heterocycle, aryl, and heteroaryl.
16. The compound of claim 14 , wherein R 351 is (R)-(tetrahydrofuran-2-yl)methyl or (S)-(tetrahydrofuran-2-yl)methyl.
17. The compound of claim 1 , having a formula selected from
or a pharmaceutically acceptable salt thereof.
18. The compound of claim 1 , having a formula selected from
or a pharmaceutically acceptable salt thereof.
19. The compound of claim 1 , having a formula selected from
or a pharmaceutically acceptable salt thereof.