Isoxazole derivatives as fxr agonists and methods of use thereof

A compound represented by Formula I, or a pharmaceutically acceptable salt thereof:

• wherein:
• R1 is hydrogen, halogen, cyano, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C6 cycloalkyl or optionally substituted 3- to 6-membered heterocycloalkyl;
• R2 is an optionally substituted aryl, optionally substituted heteroaryl, optionally substitutedarylalkyl or optionally substituted heteroarylalkyl;
• X1, X2, X3, and X4 are independently selected from N or C(Y);
• wherein Y is selected from hydrogen, halo, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, heterocycloalkyl, haloalkyl, alkoxy, or haloalkoxy;
• is aryl, heterocyclic, heteroaryl, bicyclic fused arylheterocyclic or bicyclic fused heteroarylheterocyclic, wherein said aryl, heterocyclic, heteroaryl, bicyclic fused arylheterocyclic or bicyclic fused heteroarylheterocyclic is optionally substituted with one or two substituents independently selected from optionally substituted —C1-C8 alkyl, halo, and halo-C1-C8-alkyl;
• R3 is
• R4, and R5 are independently selected from the group consisting of:
• 1) Hydrogen;
• 2) Optionally substituted —C1-C8 alkyl;
• 3) Optionally substituted —C2-C8 alkenyl;
• 4) Optionally substituted —C2-C8 alkynyl;
• and
• 5) Optionally substituted —C3-C8 cycloalkyl;
• R6 is selected from the group consisting of:
• 1) Optionally substituted —C1-C8 alkyl;
• 2) Optionally substituted —C2-C8 alkenyl;
• 3) Optionally substituted —C2-C8 alkynyl;
• 4) Optionally substituted —C3-C8 cycloalkyl;
• 5) Optionally substituted aryl;
• 6) Optionally substituted arylalkyl;
• 7) Optionally substituted 3- to 8-membered heterocycloalkyl;
• 8) Optionally substituted heteroaryl;
• 9) Optionally substituted heteroarylalkyl;
• and
• 10) NR7R8;
• wherein R7 and R8 are each independently selected from hydrogen, optionally substituted —C1-C8 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted 3- to 8-membered heterocycloalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, or R7 and R8 are taken together with the nitrogen atom which they are attached to form an optionally substituted heterocyclic ring.