THIAZOLIDINEDIONE ANALOGUES
The present invention relates to thiazolidinedione analogues that are useful for treating liver afflictions such as nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
1 . A method of treating nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) comprising administering to a patient a pharmaceutical composition comprising a compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
Each of R 1 and R 4 is independently selected from H, halo, aliphatic, and alkoxy, wherein the aliphatic and alkoxy are optionally substituted with 1-3 of halo;
R 2 is halo, hydroxy, or optionally substituted aliphatic, and R′ 2 is H, or R 2 and R′ 2 together form oxo;
R 3 is H; and
Ring A is a phenyl.
2 . (canceled)
3 . The method of claim 1 , wherein R 4 is H, methyl, methoxy, ethoxy, —O-isopropyl, —OCHF 2 or —OCF 3 .
4 . The method of claim 3 , wherein R 4 is H.
5 . The method of claim 4 , wherein R 1 is H, halo or alkoxy.
6 . The method of claim 5 , wherein R 1 is H.
7 . The method of claim 5 , wherein R 1 is halo.
8 . The method of claim 7 , wherein R 1 is attached to the para or meta position of the phenyl ring.
9 . The method of claim 7 , wherein R 1 is attached to the meta position of the phenyl ring.
10 . The method of claim 8 , wherein R 1 is F or Cl.
11 . The method of claim 5 , wherein R 1 is alkoxy.
12 . The method of claim 11 , wherein R 1 is attached to the meta or ortho position of the phenyl ring.
13 . The method of claim 11 , wherein R 1 is attached to the meta position of the phenyl ring.
14 . The method of claim 12 , wherein R 1 is methoxy, ethoxy, or —O-isopropyl.
15 . The method of claim 12 , wherein R 1 is —OCHF 2 or —OCF 3 .
16 . The method of claim 1 , wherein R′ 2 is H.
17 . The method of claim 16 , wherein R 2 is hydroxy.
18 . The method of claim 1 , wherein R 2 and R′ 2 together form oxo.
19 . The method of claim 1 , wherein the compound of formula I is
20 . The method of claim 1 , wherein the composition further comprises a diuretic, statin, angiotension II receptor blocker, a renin inhibitor, a beta adrenergic blocker, or combination thereof.
21 . The method of claim 20 , wherein the composition further comprising a glucocorticoid agonist.
22 . The method of claim 21 , wherein the glucocorticoid agonists is selected from cortisone, hydrocortisone, predisone, prednisolone, methylprednisolone, betamethasone, triameclinolone, or any combination thereof.