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:
n is 0 or 1;
Z 1 is —C(═O)—, —NH—C(═O)—or —O—C(═O)—;
R 1 is selected from the group consisting of 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 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 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 selected from the group consisting of hydrogen, an unsubstituted C 1-4 alkyl, an unsubstituted C 2-4 alkenyl, an unsubstituted C 2-4 alkynyl, an unsubstituted C 1-4 haloalkyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted cycloalkyl(C 1-4 alkyl), an optionally substituted cycloalkenyl(C 1-4 alkyl), an optionally substituted aryl(C 1-4 alkyl), an optionally substituted heteroaryl(C 1-4 alkyl), an optionally substituted heterocyclyl(C 1-4 alkyl), an optionally substituted N-amido, an optionally substituted N-sulfonamido, —NR 10 R 11 and —C(═O)NR 12 R 13 ;
R 9 is selected from the group consisting of hydrogen, an unsubstituted C 1-4 alkyl, an optionally substituted monocyclic C 4-6 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 10 and R 12 are independently hydrogen or an unsubstituted C 1-4 alkyl;
R 11 and R 13 are independently selected from the group consisting of hydrogen, an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted cycloalkyl(C 1-4 alkyl), an optionally substituted cycloalkenyl(C 1-4 alkyl), 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); or
R 10 and R 11 are taken together along with the nitrogen to which R 10 and R 11 are attached to form an optionally substituted 4- to 8-membered monocyclic heterocyclyl, an optionally substituted 8- to 13-membered fused-bicyclic heterocyclyl or an optionally substituted 7- to 13-membered spiro-bicyclic heterocyclyl;
R 12 and R 13 are taken together along with the nitrogen to which R 12 and R 13 are attached to form an optionally substituted 4- to 8-membered monocyclic heterocyclyl, an optionally substituted 8- to 13-membered fused-bicyclic heterocyclyl or an optionally substituted 7- to 13-membered spiro-bicyclic heterocyclyl;
R 2 and R 3 are taken together along with the carbon to which R 2 and R 3 are attached to form an optionally substituted monocyclic C 3-6 cycloalkyl or an optionally substituted 3 to 6 member monocyclic heterocyclyl; or
R 4 and R 5 are taken together along with the carbon to which R 4 and R 5 are attached to form an optionally substituted monocyclic C 3-6 cycloalkyl or an optionally substituted 3 to 6 member monocyclic heterocyclyl; or
R 2 and R 4 are taken together along with the carbons to which R 2 and R 4 are each attached to form an optionally monocyclic C 5-7 cycloalkyl or an optionally substituted 5 to 7 member monocyclic heterocyclyl; or
R 3 and R 5 are taken together along with the carbons to which R 3 and R 5 are each attached to form an optionally monocyclic C 5-7 cycloalkyl or an optionally substituted 5 to 7 member monocyclic heterocyclyl; or
R 6 and R 7 are taken together along with the carbon to which R 6 and R 7 are attached to form an optionally substituted monocyclic C 3-4 cycloalkyl, an optionally substituted oxetane or an optionally substituted thietane; and
X 1 is N or CR 14 , wherein R 14 is hydrogen, cyano, an unsubstituted C 1-4 alkyl, a substituted C 1-4 alkyl or an optionally substituted aryl(C 1-4 alkyl), wherein the substituted C 1-4 alkyl is substituted one or more times with a substituents selected from the group consisting of cyano, halogen, hydroxy and an unsubstituted C 1-4 alkoxy.
2. The compound of claim 1 , wherein n is 1.
3. The compound of claim 2 , wherein Z 1 is —C(═O)—.
4. The compound of claim 2 , wherein Z 1 is —NH—C(═O)—.
5. The compound of claim 1 , wherein R 1 is an optionally substituted aryl.
6. The compound of claim 5 , wherein R 1 is an optionally substituted phenyl.
7. The compound of claim 1 , wherein R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are each hydrogen.
8. The compound of claim 1 , wherein X 1 is N.
9. The compound of claim 1 , wherein X 1 is CR 14 ; and R 14 is hydrogen.
10. The compound claim 1 , wherein R 8 is hydrogen, an unsubstituted C 1-4 alkyl, an unsubstituted C 2-4 alkynyl, an optionally substituted cycloalkyl(C 1-4 alkyl), an optionally substituted aryl(C 1-4 alkyl), an optionally substituted N-amido or an optionally substituted N-sulfonamido.
11. The compound of claim 1 , wherein R 8 is —NR 10 R 11 or —C(═O)NR 12 R 13 .
12. The compound of claim 11 , wherein R 10 is hydrogen; and R 11 is an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted cycloalkyl(C 1-4 alkyl), an optionally substituted cycloalkenyl(C 1-4 alkyl), 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).
13. The compound of claim 11 , wherein R 12 is hydrogen; and R 13 is an unsubstituted C 1-4 alkyl, an unsubstituted C 1-4 haloalkyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted cycloalkyl(C 1-4 alkyl), an optionally substituted cycloalkenyl(C 1-4 alkyl), 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).
14. The compound of claim 1 , wherein R 9 is an unsubstituted C 1-4 alkyl, an optionally substituted aryl(C 1-4 alkyl), an optionally substituted heteroaryl or an optionally substituted monocyclic C 4-6 cycloalkyl.
15. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt of any of the foregoing.
16. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt of any of the foregoing.
17. A pharmaceutical composition comprising an effective amount of a compound claim 1 , or a pharmaceutically acceptable salt thereof, and excipient.
18. 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.
19. A method of claim 18 further comprising treating hepatitis D in a subject suffering from hepatitis D.
20. The method of claim 18 , 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.