Tricyclic indole derivatives and methods of use thereof
The present invention relates to Tricyclic Indole Derivatives, compositions comprising at least one Tricyclic Indole Derivatives, and methods of using the Tricyclic Indole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.
1. A compound having the formula:
and pharmaceutically acceptable salts thereof,
wherein the dotted line represents an optional and additional bond, and wherein:
R 1 is -alkylene-OC(O)-alkyl or aminoalkyl;
R 2 is H, F, Cl or —CH 3 ;
R 3 is phenyl, naphthyl, nitrogen-containing heterocycloalkyl, nitrogen-containing heterocycloalkenyl or nitrogen-containing heteroaryl, any of which can be optionally substituted with up to 3 groups, which can be the same or different, and are selected from methyl, t-butyl, allyl, F, Cl, Br, —CN, —O—CH 2 CH 3 , —S(O)CH 3 , —S(O) 2 CH 3 , —NH 2 , —OH, —CH 2 NH 2 , —C(O)NH 2 , —C(O)NHCH 3 , —C(O)NH-cyclopropyl, hydroxyalkyl, —C(O)H, —C(O)CH 3 , —C(O)O-isopropyl, —C(O)O-t-butyl, —CH 2 C(O)-t-butyl, —OCH 3 , —NHCH 3 , —SCH 3 , —C(O)NHCH 3 , —NHC(O)OCH 3 , —NHC(O)O-isopropyl, —CH 2 N(CH 3 ) 2 , —OC(O)CH(CH 3 )NHC(O)O-t-butyl, —OC(O)CH(CH 3 )NH 2 , —C(O)O-t-butyl, —CH 2 C(O)O-t-butyl, —OCH 2 CH 2 N(CH 3 ) 2 , morpholinyl, —CH 2 OC(O)-t-butyl, —CH(═NOH), —CH(═NOCH 3 ), —NHC(O)CH 2 N(CH 3 ) 2 and —NHC(O)O-t-butyl.
2. The compound of claim 1 , wherein R 1 is H or aminoalkyl.
3. The compound of claim 2 , wherein R 1 is —CH 2 CH 2 NH 2 , —CH 2 CH(NH 2 )CH 3 , —CH 2 CH 2 CH 2 NH 2 , —CH 2 CH 2 NHCH 3 , —CH 2 CH 2 N(CH 3 ) 2 , —CH 2 CH(N(CH 3 ) 2 )CH 3 , or —CH 2 CH 2 CH 2 N(CH 3 ) 2 .
4. The compound of claim 3 , wherein R 1 is —CH 2 CH 2 N(CH 3 ) 2 .
5. The compound of claim 1 , wherein R 2 is H or F.
6. The compound of claim 2 , wherein R 2 is H or F.
7. The compound of claim 1 , wherein R 3 is nitrogen-containing heteroaryl or nitrogen-containing heterocycloalkenyl.
8. The compound of claim 7 , wherein R 3 is nitrogen-containing heteroaryl.
9. The compound of claim 8 , wherein R 3 is:
10. The compound of claim 6 , wherein R 3 is nitrogen-containing heteroaryl or nitrogen-containing heterocycloalkenyl.
11. The compound of claim 10 , wherein R 3 is nitrogen-containing heteroaryl.
12. The compound of claim 11 , wherein R 3 is:
13. The compound of claim 4 , wherein R 2 is F.
14. The compound of claim 13 , wherein R 3 is:
15. A compound having the structure:
or a pharmaceutically acceptable salt thereof.
16. A pharmaceutical composition comprising at least one compound of claim 1 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.
17. The pharmaceutical composition of claim 16 , further comprising at least one additional antiviral agent, wherein the additional agent is not a compound of claim 1 , and wherein the additional antiviral agents) are selected from: an HCV polymerase inhibitor; an interferon; a RNA replication inhibitor; an antisense agent; a therapeutic vaccine; a protease inhibitor; an antibody therapy (monoclonal or polyclonal); and ribavirin.
18. A compound having the structure
or a pharmaceutically acceptable salt thereof.
19. A pharmaceutical composition comprising the compound of claim 18 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.