Multicyclic compounds and methods of use thereof

1. A compound of formula (IVa):

or a pharmaceutically acceptable salt or stereoisomer thereof, wherein

(i) R 1 and R 3 together with the atoms to which they are attached form a monocyclic 3-to 8-membered heterocyclyl optionally substituted with C 1-6 alkyl, and R 4 is hydrogen or C 1-6 alkyl; or (ii) R 3 and R 4 together form a double bond and together with R 1 and the atoms to which they are attached form an monocyclic 5- or 6-membered heteroaryl optionally substituted with C 1-6 alkyl;

R 2 is hydrogen, alkyl or absent;

R 5 is hydrogen or alkyl;

R 6 and R 7 are each independently (i) hydrogen, halo, C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 aminoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl C 1-6 alkyl, C 6-20 aryl, or C 6-20 aryl C 1-20 alkyl, wherein said C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 aminoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 3-7 cycloalkyl C 1-6 alkyl, C 6-20 aryl, or C 6-20 aryl C 1-20 alkyl is optionally substituted with halo; or (ii) —(CH 2 ) p —R 11 , wherein R 11 is CF 3 , CN, nitro, amino, hydroxyl, C 3-7 cycloalkoxyl, monocyclic 5- or 6-membered heteroaryl, or monocyclic 3- to 8-membered heterocyclyl, wherein said monocyclic 5- or 6-membered heteroaryl, monocyclic 3- to 8-membered heterocyclyl, or C 3-7 cycloalkoxyl is optionally substituted with one or more halo, C 1-6 alkyl, C 1-6 alkoxy, or phenyl;

m is 0, 1, or 2;

n is 0, 1, or 2; and

each occurrence of p is independently 0, 1, or 2.

2. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein m is 0.

3. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein n is 1.

4. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 6 and R 7 are each independently hydrogen, fluoro, chloro, methyl, CF 3 , ethyl, propyl, isopropyl, phenyl, pyridyl, pyrrolidinyl, piperidinyl, morpholinyl, methoxyl, or dimethylamino.

5. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 5 is hydrogen.

6. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R l and R 3 together with the atoms to which they are attached form an optionally substituted pyrrolidinyl; and R 4 is hydrogen or alkyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 3 and R 4 together form a double bond and together with R 1 and the atoms to which they are attached form an optionally substituted imidazoyl, pyrazolyl, or thiazolyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 1 and R 3 together with the atoms to which they are attached form monocyclic 3- to 8-membered heterocyclyl optionally substituted with C 1-6 alkyl; and R 4 is hydrogen or alkyl.

9. The compound of claim 8 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 4 is hydrogen.

10. The compound of claim 9 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 5 is hydrogen.

11. The compound of claim 10 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 6 and R 7 are each independently hydrogen, fluoro, chloro, methyl, CF 3 , ethyl, propyl, isopropyl, phenyl, pyridyl, pyrrolidinyl, piperidinyl, morpholinyl, methoxyl, or dimethylamino.

12. The compound of claim 11 , or a pharmaceutically, acceptable salt or stereoisomer thereof, wherein R 2 is hydrogen or methyl.

13. The compound of claim 12 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 2 is hydrogen.

14. The compound of claim 12 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein m is 0.

15. The compound of claim 14 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein n is 1.

16. The compound of claim 15 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 3 and R 1 together with the atoms to which they are attached form an optionally substituted pyrrolidinyl.

17. The compound of claim 8 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

18. The compound of claim 8 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

19. The compound of claim 8 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

20. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 3 and R 4 together form a double bond and together with R 1 and the atoms to which they are attached form monocyclic 5- or 6-membered heteroaryl optionally substituted with C 1-6 alkyl.

21. The compound of claim 20 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 5 is hydrogen.

22. The compound of claim 21 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 6 and R 7 are each independently hydrogen, fluoro, chloro, methyl, CF 3 , ethyl, propyl, isopropyl, phenyl, pyridyl, pyrrolidinyl, piperidinyl, morpholinyl, methoxyl, or dimethylamino.

23. The compound of claim 22 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 2 is hydrogen or methyl.

24. The compound of claim 23 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein m is 0.

25. The compound of claim 24 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein n is 1.

26. The compound of claim 25 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 3 and R 4 together form a double bond and together with R 1 and the atoms to which they are attached form imidazoyl, pyrazolyl, or thiazolyl, each optionally substituted with C 1-6 alkyl.

27. The compound of claim 20 , wherein the compound is:

or a pharmaceutically acceptable salt or stereoisomer thereof.

28. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient or carrier.

29. A method of treating neurological disorder, comprising administering to a subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the neurological disorder is schizophrenia spectrum disorder, delusional disorder, psychosis, psychotic disorder, delirium, Tourette's syndrome, post-traumatic stress disorder, behavior disorder, affective disorder, depression, major depressive disorder, dysthymia, bipolar disorder, manic disorder, seasonal affective disorder, obsessive-compulsive disorder, narcolepsy, substance abuse or dependency, Lesche-Nyhane disease, Wilson's disease, autism, or Huntington's chorea.

30. The method according to claim 29 , wherein said schizophrenia spectrum disorder is selected from schizophrenia, schizoid personality disorder, and schizotypal personality disorder.

31. The method according to claim 30 , wherein said schizophrenia is selected from acute schizophrenia and chronic schizophrenia.

32. The method according to claim 29 , wherein said psychosis is selected from organic psychosis, drug-induced psychosis, Parkinson's psychosis, and excitative psychosis.

33. The method according to claim 29 , wherein said psychotic disorder is selected from brief psychotic disorder, shared psychotic disorder, and psychotic disorder due to a general medical condition.

34. A pharmaceutical composition comprising a compound of claim 27 , or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient or carrier.

35. A method of treating neurological disorder, comprising administering to a subject a therapeutically effective amount of a compound of claim 27 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the neurological disorder is schizophrenia spectrum disorder, delusional disorder, psychosis, psychotic disorder, delirium, Tourette's syndrome, post-traumatic stress disorder, behavior disorder, affective disorder, depression, major depressive disorder, dysthymia, bipolar disorder, manic disorder, seasonal affective disorder, obsessive-compulsive disorder, narcolepsy, substance abuse or dependency, Lesche-Nyhane disease, Wilson's disease, autism, or Huntington's chorea.

36. The method according to claim 35 , wherein said schizophrenia spectrum disorder is selected from schizophrenia, schizoid personality disorder, and schizotypal personality disorder.

37. The method according to claim 36 , wherein said schizophrenia is selected from acute schizophrenia and chronic schizophrenia.

38. The method according to claim 35 , wherein said psychosis is selected from organic psychosis, drug-induced psychosis, Parkinson's psychosis, and excitative psychosis.

39. The method according to claim 35 , wherein said psychotic disorder is selected from brief psychotic disorder, shared psychotic disorder, and psychotic disorder due to a general medical condition.

40. A compound of formula:

or a pharmaceutically acceptable salt or stereoisomer thereof.

41. A compound of claim 40 , or a pharmaceutically acceptable salt thereof, selected from:

or a mixture of two or more thereof.

42. A pharmaceutical composition comprising a compound of claim 40 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

43. A method of treating neurological disorder, comprising administering to a subject a therapeutically effective amount of a compound of claim 40 , or a pharmaceutically acceptable salt thereof, wherein the neurological disorder is schizophrenia spectrum disorder, delusional disorder, psychosis, psychotic disorder, delirium, Tourette's syndrome, post-traumatic stress disorder, behavior disorder, affective disorder, depression, major depressive disorder, dysthymia, bipolar disorder, manic disorder, seasonal affective disorder, obsessive-compulsive disorder, narcolepsy, substance abuse or dependency, Lesche-Nyhane disease, Wilson's disease, autism, or Huntington's chorea.

44. The method according to claim 43 , wherein said schizophrenia spectrum disorder is selected from schizophrenia, schizoid personality disorder, and schizotypal personality disorder.

45. The method according to claim 44 , wherein said schizophrenia is selected from acute schizophrenia and chronic schizophrenia.

46. The method according to claim 43 , wherein said psychosis is selected from organic psychosis, drug-induced psychosis, Parkinson's psychosis, and excitative psychosis.

47. The method according to claim 43 , wherein said psychotic disorder is selected from brief psychotic disorder, shared psychotic disorder, and psychotic disorder due to a general medical condition.

48. A compound of formula:

or a pharmaceutically acceptable salt thereof.

49. A pharmaceutical composition comprising a compound of claim 48 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

50. A method of treating neurological disorder, comprising administering to a subject a therapeutically effective amount of a compound of claim 48 , or a pharmaceutically acceptable salt thereof, wherein the neurological disorder is schizophrenia spectrum disorder, delusional disorder, psychosis, psychotic disorder, delirium, Tourette's syndrome, post-traumatic stress disorder, behavior disorder, affective disorder, depression, major depressive disorder, dysthymia, bipolar disorder, manic disorder, seasonal affective disorder, obsessive-compulsive disorder, narcolepsy, substance abuse or dependency, Lesche-Nyhane disease, Wilson's disease, autism, or Huntington's chorea.

51. The method according to claim 50 , wherein said schizophrenia spectrum disorder is selected from schizophrenia, schizoid personality disorder, and schizotypal personality disorder.

52. The method according to claim 51 , wherein said schizophrenia is selected from acute schizophrenia and chronic schizophrenia.

53. The method according to claim 50 , wherein said psychosis is selected from organic psychosis, drug-induced psychosis, Parkinson's psychosis, and excitative psychosis.

54. The method according to claim 50 , wherein said psychotic disorder is selected from brief psychotic disorder, shared psychotic disorder, and psychotic disorder due to a general medical condition.

55. A pharmaceutical composition comprising a compound or a mixture of claim 41 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

56. A method of treating neurological disorder, comprising administering to a subject a therapeutically effective amount of a compound or a mixture of claim 41 , or a pharmaceutically acceptable salt thereof, wherein the neurological disorder is schizophrenia spectrum disorder, delusional disorder, psychosis, psychotic disorder, delirium, Tourette's syndrome, post-traumatic stress disorder, behavior disorder, affective disorder, depression, major depressive disorder, dysthymia, bipolar disorder, manic disorder, seasonal affective disorder, obsessive-compulsive disorder, narcolepsy, substance abuse or dependency, Lesche-Nyhane disease, Wilson's disease, autism, or Huntington's chorea.

57. The method according to claim 56 , wherein said schizophrenia spectrum disorder is selected from schizophrenia, schizoid personality disorder, and schizotypal personality disorder.

58. The method according to claim 57 , wherein said schizophrenia is selected from acute schizophrenia and chronic schizophrenia.

59. The method according to claim 56 , wherein said psychosis is selected from organic psychosis, drug-induced psychosis, Parkinson's psychosis, and excitative psychosis.

60. The method according to claim 56 , wherein said psychotic disorder is selected from brief psychotic disorder, shared psychotic disorder, and psychotic disorder due to a general medical condition.