4-Phenyl substituted tetrahydroisoquinolines and therapeutic use thereof

1. A method of treating a subject with depression, said method comprising:

administering to the subject a compound of Formula IA, IB, IIA, IIB, IIIA, or IIIB:

wherein:

is a single or double bond;

R 1 is selected from the group consisting of 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 and benzyl, each of which is optionally substituted with 1 to 3 substituents independently selected at each occurrence from C 1 -C 3 alkyl, halogen, —CN, —OR 8 and —NR 8 R 9 ;

R 2 is selected from the group consisting of 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 and C 1 -C 6 haloalkyl;

R 3 is selected from the group consisting of H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl and C 3 -C 6 cycloalkyl, wherein C 1 -C 6 alkyl, C 1 -C 6 haloalkyl and C 3 -C 6 cycloalkyl are optionally substituted with 1 to 3 substituents selected independently at each occurrence from OR 8 and NR 8 R 9 ;

R 4 , R 5 and R 6 are each independently selected at each occurrence thereof from the group consisting of H, halogen, —OR 10 , —NO 2 , NR 10 R 11 , —NR 10 C(O)R 11 , —NR 10 C(O)NR 11 R 12 , —S(O) n R 11 , —CN, —C(O)R 11 , —C(O) 2 R 11 , —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, 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 are optionally substituted with 1 to 3 substituents independently selected at each occurrence from C 1 -C 3 alkyl, halogen, ═O, —CN, —OR 8 , —NR 8 R 9 and phenyl, and wherein phenyl is optionally substituted with 1-3 substituents selected independently at each occurrence from halogen, —CN, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, —OR 8 and —NR 8 R 9 ; alternatively R 5 and R 6 are —O—C(R 11 ) 2 —O—;

R 7 is selected from the group consisting of H, halogen and OR 10 ;

R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 1 -C 4 alkoxyalkylalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 12 , phenyl and benzyl, wherein phenyl and benzyl are optionally substituted with 1 to 3 substituents selected independently at each occurrence from halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy;

R 10 is selected from the group consisting of 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 12 , phenyl and benzyl, wherein phenyl and benzyl are optionally substituted with 1 to 3 substituents selected independently at each occurrence from halogen, —NH 2 , —OH, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy;

R 11 is selected from the group consisting of 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 and benzyl, where phenyl and benzyl are optionally substituted with 1 to 3 substituents selected independently at each occurrence from halogen, —NH 2 , —OH, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy;

R 12 is selected from the group consisting of C 1 -C 4 alkyl, C 1 -C 4 haloalkyl and phenyl;

X is selected from the group consisting of O, NR 13 and S, with the proviso that X is not NR 13 when a compound is of Formula (IA);

n is 0, 1, or 2; and,

R 13 is selected from the group consisting of H, C 1 -C 6 alkyl, benzyl and phenyl, wherein C 1 -C 6 alkyl, benzyl and phenyl are optionally substituted with 1-3 substituents selected independently at each occurrence from halogen, —NH 2 , —OH, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy,

or a pharmaceutically acceptable salt thereof under conditions effective to treat the subject for depression.

2. The method according to claim 1 , wherein the subject is a human.

3. The method according to claim 1 , wherein R 1 is C 1 -C 6 alkyl.

4. The method according to claim 3 , wherein R 1 is CH 3 .

5. The method according to claim 1 , wherein R 2 is H, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or C 1 -C 6 haloalkyl.

6. The method according to claim 5 , wherein R 2 is H.

7. The method according to claim 6 , wherein R 2 is H.

8. The method according to claim 1 , wherein R 3 is at each occurrence thereof independently H, halogen, C 1 -C 6 alkyl, or C 1 -C 6 alkyl substituted with from 1 to 3 of OR 8 or NR 8 R 9 .

9. The method according to claim 8 , wherein R 3 is H or C 1 -C 6 alkyl.

10. The method according to claim 9 , wherein R 3 is H.

11. The method according to claim 1 , wherein R 1 is CH 3 , R 2 is H and R 3 is H.

12. The method according to claim 1 , wherein R 4 , R 5 and R 6 are each independently H, halogen, C 1 -C 6 alkyl or —OR 10 .

13. The method according to claim 12 , wherein at least one of R 4 , R 5 and R 6 is H.

14. The method according to claim 13 , wherein each of R 4 , R 5 and R 6 are H.

15. The method according to claim 12 , wherein one of R 4 , R 5 and R 6 is halogen.

16. The method according to claim 1 , wherein R 1 is CH 3 , R 2 and R 3 are each H, and at least one of R 4 , R 5 and R 6 is H.

17. The method according to claim 1 , wherein the compound is a compound of Formula (10):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (10) wherein R 4 is H, R 6 is H and R 6 is H;

a compound of Formula (10) wherein R is H, R is Me and R 6 is H;

a compound of Formula (10) wherein R 4 is C 1 , R 5 is H and R 6 is H; and

a compound of Formula (10) wherein R 4 is H, R 5 is F and R 6 is H.

18. The method according to claim 1 , wherein the compound is a compound of Formula (20):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (20) wherein R 4 is H, R 5 is H and R 6 is H;

a compound of Formula (20) wherein R 4 is H, R 5 is Me and R 6 is H;

a compound of Formula (20) wherein R 4 is H, R 5 is Cl and R 6 is H;

a compound of Formula (20) wherein R 4 is H, R 5 is F and R 6 is H; and

a compound of Formula (20) wherein R 4 is F, R 5 is H and R 6 is F.

19. The method according to claim 1 , wherein the compound is a compound of Formula (30):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is H and R 6 is H;

a compound of Formula (30) wherein R 3 is H, R 4 is F, R 5 is F and R 6 is H;

a compound of Formula (30) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is F;

a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is F and R 6 is H;

a compound of Formula (30) wherein R 3 is H, R 4 is Cl, R 5 is H and R 6 is H;

a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is Cl and R 6 is H;

a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is Cl and R 6 is F;

a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is F and R 6 is Cl;

a compound of Formula (30) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is Cl;

a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is OMe and R 6 is H; and

a compound of Formula (30) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is H.

20. The method according to claim 1 , wherein the compound is a compound of Formula (40):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (40) wherein R 3 is H, R 4 is H, R 5 is H and R 6 is H;

a compound of Formula (40) wherein R 3 is H, R 4 is F, R 5 is F and R 6 is H;

a compound of Formula (40) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is F;

a compound of Formula (40) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is H;

a compound of Formula (40) wherein R 3 is H, R 4 is H, R 5 is F and R 6 is H;

a compound of Formula (40) wherein R 3 is H, R 4 is Cl, R 5 is H and R 6 is H;

a compound of Formula (40) wherein R 3 is H, R 4 is H, R 5 is CH and R 6 is H;

a compound of Formula (40) wherein R 3 is H, R 4 is H, R 5 is Cl and R 6 is F;

a compound of Formula (40) wherein R 3 is H, R 4 is H, R 5 is F and R 6 is Cl;

a compound of Formula (40) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is CL;

a compound of Formula (40) wherein R 3 is H, R 4 is H, R 5 is OMe and R 6 is H;

a compound of Formula (40) wherein R 3 is Me, R 4 is H, R 5 is H and R 6 is H;

a compound of Formula (40) wherein R 3 is Et, R 4 is H, R 5 is H and R 6 is H; and

a compound of Formula (40) wherein R 3 is CH 2 OH, R 4 is H, R 5 is H and R 6 is H.

21. The method according to claim 1 , wherein the compound is a compound of Formula (50):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (50) wherein R 3 is H, R 4 is H, R 5 is H and R 6 is H.

22. The method according to claim 1 , wherein the compound is a compound of Formula (60):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is H;

a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is Me;

a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is Et;

a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is F and R 13 is H;

a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is F and R 13 is Me;

a compound of Formula (60) wherein R 3 is H, R 4 is F, R 5 is H, R 6 is F and R 13 is H;

a compound of Formula (60) wherein R 3 is H, R 4 is F, R 5 is H, R 6 is F and R 13 is Me;

a compound of Formula (60) wherein R 3 is H, R 4 is Cl, R 5 is H, R 6 is H and R 13 is H;

a compound of Formula (60) wherein R 3 is H, R 4 is Cl, R 5 is H, R 6 is H and R 13 is Me;

a compound of Formula (60) wherein R 3 is H, R 4 is F, R 5 is H, R 6 is H and R 13 is H;

a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is H and R 13 is H;

a compound of Formula (60) wherein R 3 is H, R 4 is F, R 5 is Cl, R 6 is H and R 13 is H;

a compound of Formula (60) wherein R 3 is H, R 4 is F, R 5 is Cl, R 6 is H and R 13 is Me;

a compound of Formula (60) wherein R 3 is H, R 4 is Cl, R 5 is F, R 6 is H and R 13 is H; and

a compound of Formula (60) wherein R 3 is H, R 4 is Cl, R 5 is F, R 6 is H and R 13 is Me.

23. The method according to claim 1 , wherein the compound is a compound of Formula (70):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is H;

a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is Me;

a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is Et;

a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is Bn;

a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is F and R 13 is H;

a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is F and R 13 is Me;

a compound of Formula (70) wherein R 3 is H, R 4 is F, R 5 is H, R 6 is F and R 13 is Me;

a compound of Formula (70) wherein R 3 is H, R 4 is Cl, R 5 is H, R 6 is H and R 13 is H;

a compound of Formula (70) wherein R 3 is H, R 4 is Cl, R 5 is H, R 6 is H and R 13 is Me;

a compound of Formula (70) wherein R 3 is H, R 4 is F, R 5 is H, R 6 is H and R 13 is H;

a compound of Formula (70) wherein R 3 is H, R 4 is F, R 5 is H, R 6 is H and R 13 is Me;

a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is H and R 13 is H;

a compound of Formula (70) wherein R 3 is H, R 4 is F, R 5 is Cl, R 6 is H and R 13 is H;

a compound of Formula (70) wherein R 3 is H, R 4 is F, R 5 is Cl, R 6 is H and R 13 is Me;

a compound of Formula (70) wherein R 3 is H, R 4 is Cl, R 5 is F, R 6 is H and R 13 is H; and

a compound of Formula (70) wherein R 3 is H, R 4 is Cl, R 5 is F, R 6 is H and R 13 is Me.

24. The method according to claim 1 , wherein the compound is a compound of Formula (80):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (80) wherein R 4 is H, R 5 is H and R 6 is H;

a compound of Formula (80) wherein R 4 is H, R 5 is F and R 6 is H; and

a compound of Formula (80) wherein R 4 is H, R 5 is F and R 6 is F.

25. The method according to claim 1 , wherein the compound is a compound of Formula (90):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (90) wherein R 4 is H, R 5 is H and R 6 is H.

a compound of Formula (90) wherein R 4 is H, R 5 is F and R 6 is F; and

a compound of Formula (90) wherein R 4 is H, R 5 is F and R 6 is H.

26. The method according to claim 1 , wherein the compound is a compound of Formula (100):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (100) wherein R 4 is H, R 5 is H, R 6 is H and R 13 is H.

27. The method according to claim 1 , wherein the compound is a compound of Formula (110):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (110) wherein R 4 is H, R 5 is H and R 6 is H;

a compound of Formula (110) wherein R 4 is H, R 5 is F and R 6 is F;

a compound of Formula (110) wherein R 4 is H, R 5 is F and R 6 is H;

a compound of Formula (110) wherein R 4 is H, R 5 is H and R 6 is Cl;

a compound of Formula (110) wherein R 4 is H, R 5 is Cl and R 6 is F;

a compound of Formula (110) wherein R 4 is H, R 5 is F and R 6 is Cl; and

a compound of Formula (110) wherein R 4 is H, R 5 is OMe and R 6 is H.

28. The method according to claim 1 , wherein the compound is a compound of Formula (120):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (120) wherein R 4 is H, R 5 is H and R 6 is H;

a compound of Formula (120) wherein R 4 is H, R 5 is F and R 6 is F;

a compound of Formula (120) wherein R 4 is H, R 5 is F and R 6 is H;

a compound of Formula (120) wherein R 4 is H, R 5 is H and R 6 is Cl;

a compound of Formula (120) wherein R 4 is H, R 5 is Cl and R 6 is F;

a compound of Formula (120) wherein R 4 is H, R 5 is OMe and R 6 is H; and

a compound of Formula (120) wherein R 4 is H, R 5 is F and R 6 is Cl.

29. The method according to claim 1 , wherein the compound is a compound of Formula (130):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (130) wherein R 4 is H, R 5 is H and R 6 is H; and

a compound of Formula (130) wherein R 4 is H, R 5 is Bn and R 6 is H.

30. The method according to claim 1 , wherein the compound is a compound of Formula (140):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (140) wherein R 4 is H, R 5 is H and R 6 is H;

a compound of Formula (140) wherein R 4 is H, R 5 is F and R 6 is H;

a compound of Formula (140) wherein R 4 is H, R 5 is F and R 6 is Cl;

a compound of Formula (140) wherein R 4 is H, R 5 is Cl and R 6 is F;

a compound of Formula (140) wherein R 4 is H, R 5 is H and R 6 is Cl;

a compound of Formula (140) wherein R 4 is H, R 5 is OMe and R 6 is H; and

a compound of Formula (140) wherein R 4 is H, R 5 is F and R is F.

31. The method according to claim 1 , wherein the compound is a compound of Formula (150):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (150) wherein R 4 is H, R 5 is H and R 6 is H;

a compound of Formula (150) wherein R 4 is H, R 5 is F and R 6 is H;

a compound of Formula (150) wherein R 4 is H, R 5 is F and R 6 is Cl;

a compound of Formula (150) wherein R 4 is H, R 5 is Cl and R 6 is F;

a compound of Formula (150) wherein R 4 is H, R 5 is H and R 6 is Cl;

a compound of Formula (150) wherein R 4 is H, R 5 is OMe and R 6 is H; and

a compound of Formula (150) wherein R 4 is H, R 5 is F and R 6 is F.

32. The method according to claim 1 , wherein the compound is a compound of Formula (160):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (160) wherein R 4 is H, R 5 is H and R 6 is H.

33. The method according to claim 1 , wherein the compound is a compound of Formula (170):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (170) wherein R 4 is H, R 5 is H and R 6 is H;

a compound of Formula (170) wherein R 4 is H, R 5 is F and R 6 is H; and

a compound of Formula (170) wherein R 4 is H, R 5 is F and R 6 is F.

34. The method according to claim 1 , wherein the compound is a compound of Formula (180):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (180) wherein R 4 is H, R 5 is H and R 6 is H;

a compound of Formula (180) wherein R 4 is H, R 5 is F and R 6 is H; and

a compound of Formula (180) wherein R 4 is H, R 5 is F and R 6 is F.

35. The method according to claim 1 , wherein the compound is a compound of Formula (190):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (190) wherein R 4 is H, R 5 is H and R 6 is H.

36. The method according to claim 1 , wherein the compound is a compound of Formula (200):

or a pharmaceutically acceptable salt form thereof selected from the group consisting of:

a compound of Formula (200) wherein R 4 is H, R 5 is H and R 6 is H and R 13 is H; and

a compound of Formula (200) wherein R 4 is H, R 5 is H and R 6 is H and R 13 is Me.

37. The method according to claim 1 , wherein the compound is selected from the group consisting of:

(R)—2—methyl—4—phenyl—1,2,3,4,8,9—hexahydro—furo[2,3—h]isoquinoline;

(S)—2—methyl—4—phenyl—1,2,3,4,8,9—hexahydro—furo[2,3—h]isoquinoline;

(R)—7—methyl—5—phenyl—5,6,7,8—tetrahydro—furo[3,2—g]isoquinoline;

(S)—7—methyl—5—phenyl—5,6,7,8—tetrahydro—furo[3,2—g]isoquinoline;

(R)—4—(4—fluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(S)—4—(4—fluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(R)—4—(3,4—difluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(S)—4—(3,4—difluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo [2,3—h]isoquinoline;

(R)—2—methyl—4—phenyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(S)—2—methyl—4—phenyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(R)—4—(4—chloro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(S)—4—(4—chloro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(R)—8—methyl—6—phenyl—2,3,6,7,8,9—hexahydro—furo[3,2—h]isoquinoline;

(S)—8—methyl—6—phenyl—2,3,6,7,8,9—hexahydro—furo[3,2—h]isoquinoline;

(R)—4—(4—fluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(S)—4—(4—fluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(R)—4—(3,5—difluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(S)—4—(3 ,5—difluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo [2,3—h]isoquinoline;

(R)—2—methyl—4—phenyl—2,3,4,7—tetrahydro—1H—pyrrolo[2,3—h]isoquinoline; and

(S)—2—methyl—4—phenyl—2,3,4,7—tetrahydro—1H—pyrrolo[2,3—h]isoquinoline.

38. The method according to claim 1 , wherein the compound is selected from the group consisting of:

(+)—2—methyl—4—phenyl—1,2,3,4,8,9—hexahydro—furo[2,3—h]isoquinoline;

(−)—2—methyl—4—phenyl—1,2,3,4,8,9—hexahydro—furo[2,3—h]isoquinoline;

(+)—7—methyl—5—phenyl—5,6,7,8—tetrahydro—furo[3,2—g]isoquinoline;

(−)—7—methyl—5—phenyl—5,6,7,8—tetrahydro—furo[3,2—g]isoquinoline;

(+)—4—(4—fluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(−)—4—(4—fluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(+)—4—(3,4—difluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(−)—4—(3,4—difluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(+)—2—methyl—4—phenyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(−)—2—methyl—4—phenyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(+)—4—(4—chloro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(−)—4—(4—chloro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(+)—8—methyl—6—phenyl—2,3,6,7,8,9—hexahydro—furo[3,2—h]isoquinoline;

(−)—8—methyl—6—phenyl—2,3,6,7,8,9—hexahydro—furo[3,2—h]isoquinoline;

(+)—4—(4—fluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(−)—4—(4—fluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(+)—4—(3,5—difluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(−)—4—(3,5—difluoro—phenyl)—2—methyl—1,2,3,4—tetrahydro—furo[2,3—h]isoquinoline;

(+)—2—methyl—4—phenyl—2,3,4,7—tetrahydro—1H—pyrrolo[2,3—h]isoquinoline; and

(−)—2—methyl—4—phenyl—2,3,4,7—tetrahydro—1H—pyrrolo[2,3—h]isoquinoline.