Liver X receptor agonists
View Patent ↗A compound of formula (I): Each of R 1 , R 2 , R 3 , R 4 , R 4′ , R 5 , R 6 , R 7 , R 11 , R 12 , R 15 , R 16 , and R 17 , independently, is hydrogen, halo, alkyl, haloalkyl, hydroxy, amino, carboxyl, oxo, sulfonic acid, or alkyl that is optionally inserted with —NH—, —N(alkyl)—, —O—, —S—, —SO—, —SO 2 —, —O—SO 2 —, —SO 2 —O—, —SO 3 —O—, —CO—, —CO—O—, —O—CO—, —CO—NR′—, or —NR′—CO—; or R 3 and R 4 together, R 4 and R 5 together, R 5 and R 6 together, or R 6 and R 7 together are eliminated so that a C═C bond is formed between the carbons to which they are attached; each of R 8 , R 9 , R 10 , R 13 , and R 14 , independently, is hydrogen, halo, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxy, or amino; n is 0, 1, or 2; A is alkylene, alkenylene, or alkynylene; and each of X, Y, and Z, independently, is alkyl, haloalkyl, —OR′, —SR′, —NR′R″, —N(OR′)R″, or —N(SR′)R″; or X and Y together are ═O, ═S, or ═NR′; wherein each of R′ and R″, independently, is hydrogen, alkyl, or haloalkyl.
1. A compound of formula (I):
in which
each of R 1 , R 2 , R 4 , R 4′ , R 5 , R 7 , R 11 , R 12 , R 15 , R 16 , and R 17 , independently, is hydrogen, halo, alkyl, haloalkyl, hydroxy, amino, carboxyl, oxo, sulfonic acid, or alkyl that is optionally inserted with —NH—, —N(alky)-, —O—, —S—, —SO—, —SO 2 —, —O—SO 2 —, —SO—O—, —SO 3 —O—, —CO—, —CO—O—, —O—CO—, —CO—NR′—, or —NR′—CO—;
each of R 3 and R 6 is hydroxy;
each of R 8 , R 9 , R 10 , R 13 , and R 14 , independently, is hydrogen, halo, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxy, or amino;
n is 0, 1, or 2;
A is alkylene, alkenylene, or alkynylene; and
one of X, Y, and Z is —OR′, and the other two are haloalkyl;
wherein R′ is hydrogen.
2. The compound of claim 1 , wherein R 5 is hydrogen, alkyl, haloalkyl, hydroxy, or amino.
3. The compound of claim 2 , wherein R 5 is H.
4. The compound of claim 1 , wherein each of R 1 , R 2 , R 4 , R 4′ , R 7 , R 8 , R 9 , R 11 , R 12 , R 14 , R 15 , R 16 , and R 17 , independently, is hydrogen, halo, alkyl, haloalkyl, hydroxy, or amino; each of R 10 and R 13 , independently, is hydrogen, alkyl, or haloalkyl; n is 0; and A is alkylene.
5. The compound of claim 4 wherein each of R 1 , R 2 , R 4 , R 4′ , R 7 , R 8 , R 9 , R 11 , R 12 , R 14 , R 15 , R 16 , and R 17 , independently, is hydrogen; and each of R 10 and R 13 , independently, is alkyl; and A is alkylene.
6. The compound of claim 1 , wherein the compound is
7. A pharmaceutical composition comprising:
an effective amount of a compound of the following formula:
in which
each of R 1 , R 2 , R 4 , R 4′ , R 5 , R 7 , R 11 , R 12 , R 15 , R 16 , and R 17 , independently, is hydrogen, halo, alkyl, haloalkyl, hydroxy, amino, carboxyl, oxo, sulfonic acid, or ailcyl that is optionally inserted with —NH—, —N(alkyl)-, —O—, —S—, —SO—, —SO 2 —, —O—SO 2 —, —SO 2 —O—, -SO 3 —O—, —CO—, —CO—O—, —O—CO—, —CO—NR′—, or —NR′—CO—;
each of R 3 and R 6 is hydroxy;
each of R 8 , R 9 , R 10 , R 13 , and R 14 , independently, is hydrogen, halo, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxy, or amino;
n is 0, 1, or 2;
A is alkylene, alkenylene, or alkynylene; and
one of X, Y, and Z is —OR′, and the other two are haloalkyl;
wherein R′ is hydrogen; and
a pharmaceutically acceptable carrier.
8. The composition of claim 7 , wherein the compound is