Tricyclic compounds
Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.
1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure:
wherein:
X is CH, CD, CF, C(CH 3 ) or N;
R 1 is a 3,4-substituted phenyl substituted with two moieties independently selected from the group consisting of —Cl, —Br, —CHF 2 , —CF 3 , —CH 3 and —CN;
R 2 and R 3 are independently selected from the group consisting of hydrogen, an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an optionally substituted C 3-4 cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted aryl(C 1-4 alkyl), an optionally substituted heteroaryl(C 1-4 alkyl) and an optionally substituted heterocyclyl(C 1-4 alkyl);
R 4 and R 5 are independently selected from the group consisting of hydrogen, an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted aryl(C 1-4 alkyl), an optionally substituted heteroaryl(C 1-4 alkyl) and an optionally substituted heterocyclyl(C 1-4 alkyl);
R 6 and R 7 are independently selected from the group consisting of hydrogen, an unsubstituted C 1-4 alkyl and an unsubstituted C 1-4 haloalkyl;
R 8 is —CHR 8a R 8b ;
R 8a is hydrogen or —CH 3 ;
R 8b is selected from the group consisting of an unsubstituted C 1-4 alkyl, an unsubstituted C 2-4 alkenyl, an unsubstituted C 2-4 alkynyl, an optionally substituted monocyclic C 3-6 cycloalkyl, an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl and an optionally substituted monocyclic heterocyclyl; and
R 9 is a substituted aryl, an optionally substituted heteroaryl or an optionally substituted heterocyclyl; and
provided that be a compound of Formula (I), or a pharmaceutically acceptable salt thereof, cannot be selected from the group consisting of:
or a pharmaceutically acceptable salt of any of the foregoing.
2. The compound of claim 1 , wherein R 1 is
3. The compound of claim 2 , wherein R 2 is an unsubstituted C 1-4 alkyl; R 3 is hydrogen; R 4 is hydrogen; R 5 is hydrogen; R 6 is hydrogen; and R 7 is hydrogen.
4. The compound of claim 2 , wherein R 2 is hydrogen; R 3 is hydrogen; R 4 is hydrogen; R 5 is hydrogen; R 6 is hydrogen; and R 7 is hydrogen.
5. The compound of claim 3 , wherein the unsubstituted C 1-4 alkyl is methyl.
6. The compound of claim 2 , wherein R 8a is hydrogen.
7. The compound of claim 6 , wherein R 8b is an unsubstituted C 1-4 alkyl.
8. The compound of claim 6 , wherein R 8b is an unsubstituted C 2-4 alkenyl or C 2-4 alkynyl.
9. The compound of claim 6 , wherein R 8b is an optionally substituted monocyclic C 3-6 cycloalkyl, an optionally substituted monocyclic heterocyclyl or an optionally substituted monocyclic heteroaryl.
10. The compound of claim 6 , wherein R 8b is an optionally substituted phenyl.
11. The compound of claim 2 , wherein R 9 is a substituted phenyl.
12. The compound of claim 11 , wherein R 9 is a substituted phenyl, wherein the phenyl is substituted with one or more substituents independently selected from the group consisting of —C(═O)NHCH 3 , halogen, an unsubstituted 5- or 6-membered monocyclic heteroaryl, a 5- or 6-membered monocyclic heteroaryl substituted with a moiety selected from the group consisting of an unsubstituted C 1-4 alkyl and a C 1-4 haloalkyl, an unsubstituted 5- or 6-membered monocyclic heterocyclyl, a 5- or 6-membered monocyclic heterocyclyl substituted with a moiety selected from the group consisting of an unsubstituted C 1-4 alkyl and a C 1-4 haloalkyl.
13. The compound of claim 2 , wherein R 9 is an optionally substituted heteroaryl.
14. The compound of claim 13 , wherein R 9 is an optionally substituted bicyclic heteroaryl.
15. The compound of claim 2 , wherein X is CH.
16. The compound of claim 1 , wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is selected from the group consisting of:
or a pharmaceutically acceptable salt of any of the foregoing.
17. The compound of claim 1 , wherein the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is selected from the group consisting of:
or a pharmaceutically acceptable salt of any of the foregoing.
18. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and excipient.
19. A method for treating hepatitis B in a subject comprising administering to the subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, suffering from hepatitis B.
20. A method for treating hepatitis D in a subject comprising administering to the subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, suffering from hepatitis D.
21. The method of claim 19 , further comprising administering an additional agent selected from the group consisting of an interferon, a nucleoside analog, a nucleotide analog, a sequence specific oligonucleotide, a nucleic acid polymer, an entry inhibitor and a small molecule immunomodulator.