Bile acid derivatives as FXR agonists and methods of use thereof

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

• is
• Ra and Rb 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,
• 5) Optionally substituted —C3-C8 cycloalkyl,
• 6) Optionally substituted aryl,
• 7) Optionally substituted arylalkyl,
• 8) Optionally substituted 3- to 8- membered heterocycloalkyl,
• 9) Optionally substituted heteroaryl, and
• 10) Optionally substituted heteroarylalkyl;
• m is selected from 1, 2 or 3;
• R1 is optionally substituted C1-C6 alkyl, hydrogen, hydroxyl, —OSO3H, —OSO3−, —OAc, —OPO3H2 or —OPO32−;
• R2 is optionally substituted C1-C6 alkyl, hydrogen, halogen, CN, N3, hydroxyl, —OSO3H, —OSO3−, —OAc, —OPO3H2, —OPO32−, —SRa or —NHRa, wherein Ra is previously defined;
• alternatively, R1 and R2 are taken together with the carbon atoms to which they attached to form —CH═CH— or cycloalkyl ring or heterocycloalkyl ring;
• R3a and R3b are independently selected from hydrogen, hydroxyl, optionally substituted C1-C6 alkyl, or optionally substituted —O—C1-C6 alkyl;
• alternatively, R3a and R3b are taken together with the carbon atom to which they attached to form —C(O);
• and
• R4 is selected from the group consisting of:
• 1) Hydrogen,
• 2) Halogen,
• 3) Optionally substituted —C1-C8 alkyl,
• 4) Optionally substituted —C2-C8 alkenyl,
• 5) Optionally substituted —C2-C8 alkynyl, and
• 6) Optionally substituted —C3-C8 cycloalkyl.