TGR5 modulators and methods of use thereof
The invention relates to compounds of Formula A: or a salt, solvate, or hydrate thereof. The compounds of formula A are TGR5 modulators useful for the treatment of disease.
1. A compound of formula A:
or a salt thereof, wherein:
R 1 is hydrogen, hydroxy, substituted or unsubstituted alkyl, or halogen;
R 2 is hydrogen or a-hydroxy;
R 4 is substituted or unsubstituted alkyl, or halogen;
R 5 is hydrogen, unsubstituted alkyl, or aryl;
R 6 is hydrogen, unsubstituted or substituted alkyl, or R 5 and R 6 taken together with the carbons to which they are attached form a ring of size 3, 4, 5, or 6 atoms;
R 7 is hydrogen, substituted or unsubstituted alkyl, or hydroxy;
R 11 is hydroxyl, OSO 3 H, OSO 3 − , OCOCH 3 , OPO 3 H, OPO 3 2− or hydrogen;
R 12 is hydroxyl, OSO 3 H, OSO 3 − , OCOCH 3 , OPO 3 H, OPO 3 2− or hydrogen, or taken together R 11 and R 12 form a carbonyl;
m is 0, 1, or 2;
n is 0 or 1;
o is 0 or 1; and
p is 1; provided that
m+n+o=3 or 4 and
when m+n+o=3, then at least one of R 5 and R 6 is not hydrogen.
2. A pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable excipient.