Aryl, heteroaryl, and heterocycle substituted tetrahydroisoquinolines and use thereof
View Patent ↗Novel aryl, heteroaryl, and non-aromatic heterocyle substituted tetrahydroisoquinolines are described in the present invention. These compounds are used in the treatment of various neurological and physiological disorders. Methods of making these compounds are also described in the present invention.
1. A compound of formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
R 1 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, C 1 -C 6 haloalkyl, or gem-dialkyl of which each alkyl is C 1 -C 4 ;
R 2 is H, halogen, —OR 11 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, or C 4 -C 7 cycloalkylalkyl, and wherein each of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C 1 -C 3 alkyl, halogen, —CN, —OR 9 , —NR 9 R 10 , and phenyl which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 9 , or —NR 9 R 10 ;
R 3 is a heteroaryl selected from the group consisting of quinoxalinyl, thieno[2,3-b]pyrazinyl, furo [2,3-b]pyrazinyl, imidazol[1,2-a]pyrazinyl, and [1,2,4]triazolo[4,3-a]pyrazinyl; wherein the heteroaryl is optionally substituted from 1 to 4 times with substituents as defined below in R 14 ;
R 4 , R 5 , R 6 , and R 7 are independently H or are selected from the group consisting of halogen, —OR 11 , —NR 11 R 12 , —NR 11 C(O)R 12 , —NR 11 C(O) 2 R 12 , —NR 11 C(O)NR 12 R 13 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl, and wherein each of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C 1 -C 3 alkyl, halogen, —CN, —OR 9 , —NR 9 R 10 , and phenyl which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 9 , or —NR 9 R 10 ;
R 8 is H, C 1 -C 6 alkyl, halogen or OR 11 ;
R 9 and R 10 are each independently H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 13 , phenyl, or benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
or R 9 and R 10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R 11 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 13 , phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 12 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
or R 11 and R 12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R 9 and R 10 or R 11 and R 12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R 13 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or phenyl;
n is 0, 1, or 2; and
R 14 is independently selected at each occurrence from a substituent selected from the group consisting of halogen, —NO 2 , —OR 11 , —NR 11 R 12 , —NR 11 C(O)R 12 , —NR 11 C(O) 2 R 12 , —NR 11 C(O)NR 12 R 13 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl, where C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of C 1 -C 3 alkyl, halogen, Ar, —CN, —OR 9 , and —NR 9 R 10 , or
an oxide thereof, or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 1 is H, C 1 -C 6 alkyl, or gem-dialkyl of which each alkyl is C 1 -C 4 .
3. The compound of claim 2 , wherein R 1 is H or gem-dimethyl.
4. The compound of claim 1 , wherein R 2 is H, halogen, —OR 11 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl or substituted C 1 -C 6 alkyl.
5. The compound of claim 4 , wherein R 2 is H or F.
6. The compound of claim 1 , wherein R 4 is H, Cl, F, CH 3 , OH, or OCH 3 .
7. The compound of claim 1 , wherein R 4 is H or F.
8. The compound of claim 1 , wherein R 5 , R 6 , and R 7 are each independently selected from the group consisting of H, halogen, —OR 11 , —NR 11 R 12 , —NR 11 C(O)R 12 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, and substituted C 1 -C 6 alkyl.
9. The compound of claim 8 , wherein R 7 is H.
10. The compound of claim 9 , wherein R 5 and R 6 are each H, F, Cl, OH, OCH 3 , or CH 3 .
11. The compound of claim 10 , wherein R 5 and R 6 are each Cl.
12. The compound of claim 1 , wherein R 8 is H, OH, CH 3 , or F.
13. The compound of claim 1 , wherein:
R 1 is H, C 1 -C 6 alkyl, or gem-dialkyl of which each alkyl is C 1 -C 4 ;
R 2 is H, halogen, —OR 11 , —S(O) 2 R 12 , C 1 -C 6 alkyl, or substituted C 1 -C 6 alkyl;
R 4 is H, F, or Cl; and
R 5 , R 6 , and R 7 are each independently H, halogen, —OR 11 , —NR 11 R 12 , —S(O) 2 R 12 , —C(O)R 12 , C 1 -C 6 alkyl, or substituted C 1 -C 6 alkyl.
14. The compound of claim 1 , wherein:
R 1 is H or gem-dimethyl;
R 2 is H;
R 4 is H or F;
R 5 and R 6 are each independently H, F, Cl, OH, OMe, or Me;
R 7 is H or F; and
R 8 is H, OH, or F.
15. The compound of claim 1 , wherein:
R 1 is H or gem-dimethyl;
R 2 is H;
R 4 is H or F;
R 5 and R 6 are each independently H, F, Cl, or CH 3 ;
R 7 is H; and
R 8 is H.
16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound according to claim 1 .
17. A compound of formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
R 1 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, C 1 -C 6 haloalkyl, or gem-dialkyl of which each alkyl is C 1 -C 4 ;
R 2 is H, halogen, —OR 11 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, or C 4 -C 7 cycloalkylalkyl, and wherein each of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C 1 -C 3 alkyl, halogen, —CN, —OR 9 , —NR 9 R 10 , and phenyl which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 9 , or —NR 9 R 10 ;
R 3 is a heteroaryl selected from the group consisting of quinoxalinyl, thieno[2, 3-b]pyrazinyl, furo[2,3-b]pyrazinyl, imidazol[1,2-a]pyrazinyl, and [1,2,4]triazolo[4,3-a]pyrazinly; wherein the heteroaryl is optionally substituted from 1 to 4 times with substituents as defined below in R 14 ;
R 4 is selected from the group consisting of H, halogen, —NR 11 R 12 , —NR 11 C(O)R 12 , —NR 11 C(O) 2 R 12 , —NR 11 C(O)NR 12 R 13 , —SOR 12 , —S(O) 2 R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl, and wherein each of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C 1 -C 3 alkyl, halogen, —CN, —OR 9 , —NR 9 R 10 , and phenyl which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 9 , or —NR 9 R 10 ;
R 5 and R 6 and R 7 are each independently H or are selected from the group consisting of halogen, —OR 11 , —NR 11 C(O)R 12 , —NR 11 C(O) 2 R 12 , —NR 11 C(O)NR 12 R 13 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl, and wherein each of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C 1 -C 3 alkyl, halogen, —CN, —OR 9 , —NR 9 R 10 , and phenyl which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 9 , or —NR 9 R 10 ;
R 8 is H, C 1 -C 6 alkyl, halogen, or OR 11 ;
R 9 and R 10 are each independently H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 13 , phenyl, or benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
or R 9 and R 10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R 11 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 13 , phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 12 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
or R 11 and R 12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R 9 and R 10 or R 11 and R 12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R 13 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or phenyl;
n is 0, 1, or 2; and
R 14 is independently selected at each occurrence from a substituent selected from the group consisting of halogen, —NO 2 , —OR 11 , —NR 11 R 12 , —NR 11 C(O)R 12 , —NR 11 C(O) 2 R 12 , —NR 11 C(O)NR 12 R 13 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl, are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of C 1 -C 3 alkyl, halogen, Ar, —CN, —OR 9 , and —NR 9 R 10 , or
an oxide thereof, a pharmaceutically acceptable salt thereof,;
with the proviso that when R 3 is phenyl or monocyclic aromatic heterocycle, R 14 cannot be C 1 -C 6 alkyl substituted with —NR 9 R 10 .
18. The compound of claim 17 , wherein R 1 is C 1 -C 6 alkyl or gem-dialkyl.
19. The compound of claim 18 , wherein R 1 is gem-dimethyl.
20. The compound of claim 17 , wherein R 2 is H, halogen, —OR 11 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, or substituted C 1 -C 6 alkyl.
21. The compound of claim 20 , wherein R 2 is H or F.
22. The compound of claim 17 , wherein R 4 is H, Cl, F, or CH 3 .
23. The compound of claim 22 , wherein R 4 is H or F.
24. The compound of claim 17 , wherein R 5 , R 6 , and R 7 are each independently selected from the group consisting of H, halogen, —OR 11 , —NR 11 C(O)R 12 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, and substituted C 1 -C 6 alkyl.
25. The compound of claim 24 , wherein R 7 is H.
26. The compound of claim 25 , wherein R 5 and R 6 are each H, F, Cl, OH, OCH 3 , or CH 3 .
27. The compound of claim 26 , wherein R 5 and R 6 are each Cl.
28. The compound of claim 17 , wherein R 8 is H, OH, CH 3 , or F.
29. The compound of claim 17 , wherein:
R 1 is C 1 -C 6 alkyl or gem-dialkyl of which each alkyl is C 1 -C 4 ;
R 2 is H, halogen, —OR 11 , —S(O) 2 R 12 , C 1 -C 6 alkyl, or substituted C 1 -C 6 alkyl;
R 4 is H, F, or Cl; and
R 5 , R 6 , and R 7 are each independently H, halogen, —OR 11 , —S(O) 2 R 12 , —C(O)R 12 , C 1 -C 6 alkyl, or substituted C 1 -C 6 alkyl.
30. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound according to claim 17 .
31. A compound of formula (I):
wherein:
the carbon atom designated * is in the R or S configuration;
R 1 is gem-dialkyl of which each alkyl is C 1 -C 4 ;
R 2 is H, halogen, —OR 11 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, or C 4 -C 7 cycloalkylalkyl, and wherein each of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C 1 -C 3 alkyl, halogen, —CN, —OR 9 , —NR 9 R 10 , and phenyl which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 9 , or —NR 9 R 10 ;
R 3 is a heteroaryl selected from the group consisting of quinoxalinyl, thieno[2, 3-b]pyrazinyl, furo[2,3-b]pyrazinyl, imidazol[1,2-a]pyrazinyl, and [1,2,4]triazolo[4,3-a]pyrazinly; wherein the heteroaryl is optionally substituted from 1 to 4 times with substituents as defined below in R 14 ;
R 4 , R 5 , R 6 , and R 7 are independently H or are selected from the group consisting of halogen, —OR 11 , —NR 11 R 12 , —NR 11 C(O)R 12 , —NR 11 C(O) 2 R 12 , —NR 11 C(O)NR 12 R 13 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl, and wherein each of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C 1 -C 3 alkyl, halogen, —CN, —OR 9 , —NR 9 R 10 , and phenyl which is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, —CN, —OR 9 , or —NR 9 R 10 ;
R 8 is H, C 1 -C 6 alkyl, halogen, or OR 11 ;
R 9 and R 10 are each independently H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 13 , phenyl, or benzyl, where phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and C 1 -C 4 alkoxy;
or R 9 and R 10 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R 11 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 13 , phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
R 12 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl, or benzyl, where phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1 -C 4 alkoxy;
or R 11 and R 12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R 9 and R 10 or R 11 and R 12 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R 13 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or phenyl;
n is 0, 1, or 2; and
R 14 is independently selected at each occurrence from a substituent selected from the group consisting of halogen, —NO 2 , —OR 11 , —NR 11 R 12 , —NR 11 C(O)R 12 , —NR 11 C(O) 2 R 12 , —NR 11 C(O)NR 12 R 13 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl, where C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, and C 4 -C 7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from the group consisting of C 1 -C 3 alkyl, halogen, Ar, —CN, —OR 9 , and —NR 9 R 10 , or
an oxide thereof, or a pharmaceutically acceptable salt thereof.
32. The compound of claim 31 , wherein R 1 is gem-dimethyl.
33. The compound of claim 31 , wherein R 2 is H, halogen, —OR 11 , —S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, or substituted C 1 -C 6 alkyl.
34. The compound of claim 33 , wherein R 2 is H or F.
35. The compound of claim 31 , wherein R 4 is H, Cl, F, CH 3 , OH, or OCH 3 .
36. The compound of claim 35 , wherein R 4 is H or F.
37. The compound of claim 31 , wherein R 5 , R 6 , and R 7 are each independently selected from the group consisting of H, halogen, —OR 11 , —NR 11 R 12 , —NR 11 C(O)R 12 ,S(O) n R 12 , —CN, —C(O)R 12 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, and substituted C 1 -C 6 alkyl.
38. The compound of claim 37 , wherein R 7 is H.
39. The compound of claim 38 , wherein R 5 and R 6 are each H, F, Cl, OH, OCH 3 , or CH 3 .
40. The compound of claim 39 , wherein R 5 and R 6 are each Cl.
41. The compound of claim 31 , wherein R 8 is H, OH, CH 3 , or F.
42. The compound of claim 31 , wherein:
R 1 is gem-dialkyl of which each alkyl is C 1 -C 4 ;
R 2 is H, halogen, —OR 11 , —S(O) 2 R 12 , C 1 -C 6 alkyl, or substituted C 1 -C 6 alkyl;
R 4 is H, F, or Cl; and
R 5 , R 6 , and R 7 are each independently H, halogen, —OR 11 , —NR 11 R 12 , —S(O) 2 R 12 , —C(O)R 12 , C 1 -C 6 alkyl, or substituted C 1 -C 6 alkyl.
43. The compound of claim 31 , wherein:
R 1 is gem-dimethyl;
R 2 is H;
R 4 is H or F;
R 5 and R 6 are each independently H, F, Cl, OH, OMe, or Me;
R 7 is H or F; and
R 8 is H, OH, or F.
44. The compound of claim 31 , wherein:
R 1 is gem-dimethyl;
R 2 is H;
R 4 is H or F;
R 5 and R 6 are each independently H, F, Cl, or CH 3 ;
R 7 is H; and
R 8 is H.
45. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound according to claim 31 .