STAT3 inhibitors
View Patent ↗Compounds as STAT3 inhibitors are described. A pharmaceutical composition comprising the same, methods of making the same, and a method for treating or preventing conditions such as cancer, chronic inflammation, and fibrosis using the same, are described.
1. A pharmaceutical composition, comprising
(a) a compound of Formula I,
or a pharmaceutically acceptable salt thereof, wherein
each occurrence of R 1 is independently hydrogen, halogen, cyano, nitro, CF 3 , OCF 3 , OR a , SR a , C(═O)R a , OC(═O)R a , C(═O)OR a , NR b R c , NR b C(═O)R c , C(═O)NR b R c , NR b C(═O)OR c , OC(═O)NR b R c , NR a C(═O)NR b R c , alkyl, alkenyl, cycloalkyl, optionally substituted aryl, or optionally substituted heterocycle;
n 1 is 0, 1, 2, 3, or 4;
each occurrence of R 2 is independently hydrogen, halogen, cyano, nitro, CF 3 , OCF 3 , OR a , SR a , C(═O)R a , OC(═O)R a , C(═O)OR a , NR b R c , NR b C(═O)R c , C(═O)NR b R c , NR b C(═O)OR c , OC(═O)NR b R c , NR a C(═O)NR b R c , alkyl, alkenyl, cycloalkyl, cycloalkenyl, optionally substituted aryl, optionally substituted aryloxyl, or optionally substituted heterocycle;
n 2 is 0, 1, 2, 3, 4, or 5;
R 3 is hydrogen, halogen, cyano, nitro, CF 3 , OCF 3 , OR a , SR a , OC(═O)R a , alkyl, alkenyl, cycloalkyl, or optionally substituted aryl or heteroaryl;
R 4 is hydrogen, halogen, cyano, nitro, CF 3 , OCF 3 , OR a , SR a , NR b R c , OC(═O)R a , alkyl, alkenyl, or cycloalkyl;
each occurrence of R 5 , R 6 , and R 7 is independently hydrogen, halogen, cyano, nitro, CF 3 , OCF 3 , OR a , SR a , C(═O)R a , OC(═O)R a , C(═O)OR a , NR b R c , NR b C(═O)R c , C(═O)NR b R c , NR b C(═O)OR c , OC(═O)NR b R c , NR a C(═O)NR b R c , alkyl, alkenyl, cycloalkyl, optionally substituted aryl, or optionally substituted heterocycle;
n 3 is 0, 1, 2, 3, or 4; and
each occurrence of R a , R b , and R c is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl; or said R b and R c together with the nitrogen atom to which they are bonded optionally form a heterocycle comprising 1-4 heteroatoms; and
(b) a pharmaceutically acceptable excipient.
2. The pharmaceutical composition of claim 1 , wherein each occurrence of R 1 is independently hydrogen, halogen, cyano, nitro, CF 3 , OCF 3 , OR a , or SR a .
3. The pharmaceutical composition of claim 1 , wherein n 1 is 0, 1, or 2.
4. The pharmaceutical composition of claim 1 , wherein each occurrence of R 2 is independently hydrogen, halogen, cyano, nitro, CF 3 , OCF 3 , OR a , or SR a .
5. The pharmaceutical composition of claim 1 , wherein R 3 is hydrogen, halogen, cyano, nitro, or CF 3 .
6. The pharmaceutical composition of claim 1 , wherein R 4 is hydrogen, halogen, cyano, nitro, or OR a .
7. The pharmaceutical composition of claim 1 , wherein R 5 , R 6 , and R 7 are each independently selected from the group consisting of hydrogen, halogen, cyano, nitro, and CF 3 .
8. The pharmaceutical composition of claim 1 wherein the compound has the structure of Formula II:
or a pharmaceutically acceptable salt thereof.
9. The pharmaceutical composition of claim 8 , wherein R 2 is NH 2 , OH, OMe, OEt, OCH 2 CH 2 CH 3 , or OCH(CH 3 ) 2 .
10. The pharmaceutical composition of claim 8 , wherein R 3 is H, OH, alkyl, alkoxy, or halogen.
11. The pharmaceutical composition of claim 8 , wherein R 4 is H, alkyl, OH, NH 2 , alkoxy, halogen, CF 3 , or CN.