TGR5 modulators and methods of use thereof

A compound of formula D:

• or a salt or solvate thereof, wherein:
• R1 is hydrogen, hydroxy, substituted or unsubstituted alkyl, or halogen;
• R2 is hydrogen or α-hydroxy;
• R4 is substituted or unsubstituted alkyl or halogen;
• R7 is hydrogen, substituted or unsubstituted alkyl, or hydroxy;
• R11 is hydroxyl, OSO3H, OSO3−, OCOCH3, OPO3H, OPO32− or hydrogen;
• and
• R12 is hydroxyl, OSO3H, OSO3−, OCOCH3, OPO3H, OPO32− or hydrogen, or taken together R11 and R12 form a carbonyl.

A compound of formula E:

• or a salt or solvate thereof, wherein:
• R1 is hydrogen, hydroxy, substituted or unsubstituted alkyl, or halogen;
• R2 is hydrogen or α-hydroxyl;
• R4 is hydrogen, substituted or unsubstituted alkyl, or halogen;
• R5 is hydrogen, unsubstituted alkyl, or aryl;
• R6 is hydrogen, unsubstituted or substituted alkyl, or R5 and R6 taken together with the carbons to which they are attached form a ring of size 3, 4, 5, or 6 atoms;
• R7 is hydrogen, substituted or unsubstituted alkyl, or hydroxy;
• R11 is hydroxyl, OSO3H, OSO3−, OCOCH3, OPO3H, OPO32− or hydrogen;
• R12 is hydroxyl, OSO3H, OSO3−, OCOCH3, OPO3H, OPO32− or hydrogen, or taken together R11 and R12 form a carbonyl, provided that at least one of R5 or R6 is not hydrogen.

A method of ameliorating obesity in a subject comprising administering to the subject a compound of formula A or a pharmaceutically acceptable salt or solvate thereof:

• wherein:
• R1 is hydrogen, hydroxy, substituted or unsubstituted alkyl, or halogen;
• R2 is hydrogen or α-hydroxy;
• R4 is substituted or unsubstituted alkyl or halogen;
• R5 is hydrogen;
• R6 is hydrogen;
• R7 is hydrogen, substituted or unsubstituted alkyl, or hydroxy;
• R11 is hydroxyl, OSO3H, OSO3−, OCOCH3, OPO3H, OPO32− or hydrogen;
• R12 is hydroxyl, OSO3H, OSO3−, OCOCH3, OPO3H, OPO32− or hydrogen, or taken together R11 and R12 form a carbonyl;
• m is 0, 1, or 2;
• n is 0 or 1;
• o is 0 or 1;
• and
• p is 1,
• wherein m+n+o=3.