BICYCLIC-NITROGEN COMPOUNDS AS MODULATORS OF GHRELIN RECEPTOR AND USES THEREOF

• US 20070213359A1
• Filed: 12/29/2006
• Published: 09/13/2007
• Est. Priority Date: 12/30/2005
• Status: Abandoned Application

• Current Assignee: Acadia Pharmaceuticals Inc.
• Original Assignee: Acadia Pharmaceuticals Inc.
• Inventors: Olsson, Roger, Eskildsen, Jorgen, Burstein, Ethan, Ek, Fredrik, Knapp, Anne
• Application Number:
  US11/618,724
• Publication Number:
  US 20070213359A1
• Time in Patent Office: Days
• US Class Current: 514/300
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: C07D 209/12 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 209/42 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/08 linked by a carbon chain containing alicyclic rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 451/02 containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
• CPC Class Codes: C07D 451/04 with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
• CPC Class Codes: C07D 451/06 Oxygen atoms
• CPC Class Codes: C07D 451/14 containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 471/08 Bridged systems
• CPC Class Codes: C07D 471/10 Spiro-condensed systems
• CPC Class Codes: C07D 487/08 : Bridged systems
• CPC Class Codes: C07D 491/10 : Spiro-condensed systems
• CPC Class Codes: C07D 519/00 : Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

Disclosed herein are compounds of Formula I as defined herein, or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, that modulates the activity of a ghrelin receptor. Disclosed herein are also methods of treating diseases or conditions that comprise administering to a subject in need thereof a therapeutically effective amount of a compound of Formula I.

Claims

1. A compound of Formula (I):

or a solvate, a polymorph, a metabolite, or a pharmaceutically acceptable salt or prodrug thereof, wherein;

A is selected from the group consisting of hydrogen, halogen, cyano, mono-substituted, poly-substituted or unsubstituted variants of the following residues;

alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, —

C(=Z)R₁, —

C(=Z)OR₁, —

C(=Z)NR_1aR_1b, —

C(R₁)═

NR_1a, —

NR_1aR_1b, —

N═

CR_1aR_1b, —

N(R₁)—

C(=Z)R₁, —

N(R₁)—

C(=Z)NR_1aR_1b, —

S(O)NR_1aR_1b, —

S(O)₂NR_1aR_1b, —

N(R₁)—

S(═

O)R₁, —

N(R₁)—

S(═

O)₂R₁, —

OR₁, —

SR₁, and —

OC(═

O)R₁;

B is selected from the group consisting of hydrogen;

mono-substituted, poly-substituted or unsubstituted variants of the following residues;

alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, —

C(=Z)R₁, —

C(=Z)OR₁, —

C(=Z)NR_1aR_1b, —

C(=Z)N(OR_1a)R_1b, —

C(=Z)N(R₁)NR_1aR_1b, —

C(R₁)═

NR_1a, —

C≡

N;

—

NR_1aR_1b, —

N═

CR_1aR_1b, —

N(R₁)—

C(=Z)R₁, —

N(R₁)—

C(=Z)NR_1aR_1b, —

S(O)NR_1aR_1b, —

S(O)₂NR_1aR_1b, —

N(R₁)—

S(═

O)R₁, —

N(R₁)—

S(═

O)₂R₁, —

S(O)R₁, —

S(O)₂R₁, —

OR₁, —

SR₁, and —

OC(═

O)R₁;

A and B can be taken together to form an unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heteroalicyclyl;

R₁, R_1a and R_1b are each independently selected from the group consisting of hydrogen, mono-substituted, poly-substituted or unsubstituted variants of the following residues;

alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl and haloalkyl;

R₂ and R_2a are each independently selected from the group consisting of hydrogen, cyano, mono-substituted, poly-substituted or unsubstituted variants of the following residues;

alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, sulfinyl, sulfonyl, haloalkyl, —

C(=Z)R₁, —

C(=Z)OR₁, —

C(=Z)NR_1aR_1b, —

C(R₁)═

NR_1a, —

(C_1-4alkyl)-Z-aryl, —

(C_1-4alkyl)C(═

O) R₁, —

NR_1aR_1b, —

N═

CR_1aR_1b, —

N(R₁)—

C(=Z)R₁, —

N(R₁)—

C(=Z)NR_1aR_1b, —

S(O)NR_1aR_1b, —

S(O)₂NR_1aR_1b, —

N(R₁)—

S(═

O)R₁, —

N(R₁)—

S(═

O)₂R₁, —

OR₁, —

SR₁, and —

OC(=Z)R₁;

or

R₂ and R_2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl;

R₃, R_3a, R_3b, and R_3c are each independently selected from the group consisting of hydrogen, halogen, cyano, nitro, mono-substituted, poly-substituted or unsubstituted variants of the following residues;

alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, —

C(=Z)R₁, —

C(Z)OR₁, —

C(=Z)NR_1aR_1b, —

C(R₁)═

NR_1a, —

NR_1aR_1b, —

N═

CR_1aR_1b, —

N(R₁)—

C(=Z)R₁, —

N(R₁)—

C(=Z)NR_1aR_1b, —

S(O)NR_1aR_1b, —

S(O)₂NR_1aR_1b, —

N(R₁)—

S(═

O)R₁, —

N(R₁)—

S(═

O)₂R₁, —

OR₁, —

SR₁, and —

OC(=Z)R₁;

R₃, R_3a, R_3b, and R_3c can be taken together with one or more adjacent members of the group consisting of R₃, R_3a, R_3b, and R_3c to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring;

R_3c can be taken together with B to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring;

L can be a unsubstituted or substituted lower alkylene group, wherein when L is substituted, it is substituted with one or more group(s) individually and independently selected from the group consisting of alkyl, alkenyl, halogen, haloalkyl, alkoxy, haloalkoxy, hydroxyl, and —

CN;

L can be taken together with R₃ to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring;

Y is C—

R₃ or N; and

Z is O or S.

2. The compound of claim 1, wherein the compound of Formula (I) modulates, agonizes, inverse agonizes, or antagonizes a ghrelin receptor.

3. The compound of claim 1, wherein the compound of Formula (I) inverse agonizes or antagonizes a ghrelin receptor.

4. The compound of claim 1, wherein Y is C—

R₃.

5. The compound of claim 4, wherein R₃ is selected from the group consisting of hydrogen, halogen, cyano, nitro, mono-substituted, poly-substituted or unsubstituted variants of the following residues:

alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, —

C(=Z)R₁, —

C(=Z)OR₁, —

C(=Z)NR_1aR_1b, —

C(R₁)═

NR_1a, —

NR_1aR_1b, —

N═

CR_1aR_1b, —

N(R₁)—

C(=Z)R₁, —

N(R₁)—

C(=Z)NR_1aR_1b, —

S(O)NR_1aR_1b, —

S(O)₂NR_1aR_1b, —

N(R₁)—

S(═

O)R₁, —

N(R₁)—

S(═

O)₂R₁, —

OR₁, —

SR₁, and —

OC(=Z)R₁

6. The compound of claim 5, wherein R₃ is selected from the group consisting of alkyl, alkoxy, —

C≡

N, and halogen.

7. The compound of claim 6, wherein the alkyl is selected from the group consisting methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and t-butyl.

8. The compound of claim 7, wherein the alkyl is selected from the group consisting methyl and ethyl.

9. The compound of claim 6, wherein the alkoxy is selected from the group consisting methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and t-butoxy.

10. The compound of claim 9, wherein the alkoxy is methoxy.

11. The compound of claim 6, wherein R₃ is selected from the group consisting of alkyl, alkoxy, —

C≡

N, and halogen; and

B is selected from the group consisting of —

C(—

O)R₁, —

C(═

O)OR₁, —

C(=Z)NR_1aR_1b, —

C(=Z)N(OR_1a)R_1b, and —

C≡

N.

12. The compound of claim 1, wherein Y is N.

13. The compound of claim 1, wherein R_2a is selected from the group consisting mono-substituted, poly-substituted or unsubstituted variants of the following residues:

alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, —

(C_1-4alkyl)-Z-aryl, and —

(C_1-4alkyl)C(═

O)R₁.

14. The compound of claim 13, wherein the cycloalkenyl is

15. The compound of claim 13, wherein R₂ is hydrogen.

16. The compound of claim 13, wherein R₂ is an alkyl.

17. The compound of claim 1, wherein R₂ and R_2a are taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl.

18. The compound of claim 1, wherein R₂ and R_2a are taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl selected from the group consisting of:

which is unsubstituted or substituted with one or more group(s) individually and independently selected from the group consisting of hydrogen, halogen, cyano, nitro, hydroxyl, mono-substituted, poly-substituted or unsubstituted variants of the following residues;

alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heteroalicyclyl, (heteroalicyclyl)alkyl, alkoxy, aryloxy, ester, mercapto, alkylthio, arylthio, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, isocyanato, thiocyanato, isothiocyanato, C-carboxy, O-carboxy, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino.

19. The compound of claim 18, wherein R₂ and R_2a are taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl selected from the group consisting of:

which is unsubstituted or substituted with one or more group(s) individually and independently selected from the group consisting of;

wherein;

n is integer selected from the group consisting of 0, 1, 2, 3, 4, 5, and 6;

m is integer selected from the group consisting of 0, 1, 2, 3, 4, 5, and 6;

Q is oxygen or sulfur; and

R_4a, R_4b, R_4c, R_4d, R_4e, and R_f are each independently selected from the group consisting of hydrogen, halogen, cyano, nitro, hydroxyl, mono-substituted, poly-substituted or unsubstituted variants of the following residues;

alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heteroalicyclyl, (heteroalicyclyl)alkyl, alkoxy, aryloxy, ester, mercapto, alkylthio, arylthio, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, isocyanato, thiocyanato, isothiocyanato, C-carboxy, O-carboxy, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino.

20. The compound of claim 19, wherein R₂ and R_2a are taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl, which is unsubstituted or substituted with one or more group(s) individually and independently selected from the group consisting of:

21. The compound of claim 19, wherein Q is oxygen.

22. The compound of claim 19, wherein Q is sulfur.

23. The compound of claim 19, wherein R_4a, R_4b, R_4c, R_4d, and R_4e are each independently selected from the group consisting of hydrogen, halogen, cyano, nitro, hydroxyl, mono-substituted, poly-substituted or unsubstituted variants of the following residues:

alkyl, alkoxy, aryl, alkylthio, and haloalkyl.

24. The compound of claim 19, wherein at least one of R_4a, R_4b, R_4c, R_4d, and R_4e, is halogen.

25. The compound of claim 23, wherein the alkoxy is selected from the group consisting of methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and t-butoxy.

26. The compound of claim 25, wherein the alkoxy is methoxy

27. The compound of claim 23, wherein the alkyl is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and t-butyl.

28. The compound of claim 27, wherein the alkyl is selected from the group consisting of methyl and ethyl.

29. The compound of claim 23, wherein the aryl is pyridine.

30. The compound of claim 23, wherein the haloalkyl is CF₃.

31. The compound of claim 19, wherein n is an integer selected from the group consisting of 0, 1, 2, and 3.

32. The compound of claim 19, wherein m is an integer selected from the group consisting of 1, 2, and 3.

33. The compound of claim 19, wherein

is n-butyl or n-pentyl.

34. The compound of claim 18, wherein R₂ and R_2a are taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl selected from the group consisting of:

35. The compound of claim 34, wherein R₂ and R_2a are taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl selected from the group consisting of:

36. The compound of claim 1, wherein B is selected form the group consisting of —

C(—

O)R₁, —

C(—

O)OR₁, —

C(=Z)NR_1aR_1b, —

C(=Z)N(OR_1a)R_1b, and —

C≡

N

37. The compound of claim 36, wherein B is —

C(═

O)R₁.

38. The compound of claim 36, wherein B is —

C(=Z)NR_1aR_1b.

39. The compound of claim 1, wherein R₁, R_1a and R_1b are each independently selected from the group consisting of:

hydrogen, mono-substituted, poly-substituted or unsubstituted variants of the following residues;

alkyl, alkenyl, cycloalkyl, aryl, aralkyl, and haloalkyl.

40. The compound of claim 39, wherein said alkyl is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, linear or branched pentyl, linear or branched hexyl, linear or branched heptyl, and linear or branched octyl.

41. The compound of claim 40, wherein said alkyl is selected from the group consisting of methyl, ethyl, n-butyl, isobutyl, linear hexyl, and branched octyl.

42. The compound of claim 39, wherein said aryl is phenyl.

43. The compound of claim 39, wherein said cycloalkyl is cyclopropyl.

44. The compound of claim 39, wherein said haloalkyl is CF₃.

45. The compound of claim 39, wherein said aralkyl is optionally substituted phenyl(C_1-4alkyl).

46. The compound of claim 45, wherein said aralkyl is optionally substituted phenyl(methyl)

47. The compound of claim 45, wherein said optionally substituted phenyl(C_1-4alkyl) is substituted with a substituent selected from the group consisting of alkyl and halogen.

48. The compound of claim 47, wherein the optionally substituted phenyl(C_1-4alkyl) is substituted is methyl.

49. The compound of claim 1, wherein R₃, R_3a, R_3b, and R_3c are each independently selected from the group consisting of hydrogen, halogen;

mono-substituted, poly-substituted or unsubstituted variants of the following residues;

alkyl and —

OR₁.

50. The compound of claim 49, wherein said alkyl is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and t-butyl.

51. The compound of claim 49, wherein the alkyl is selected from the group consisting of methyl and ethyl.

52. The compound of claim 49, wherein R₁ is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and t-butyl.

53. The compound of claim 52, wherein R₁, is selected from the group consisting of methyl and isopropyl.

54. The compound of claim 1, wherein A is hydrogen.

55. The compound of claim 1, wherein A is alkyl.

56. The compound of claim 55, wherein the alkyl is methyl.

57. The compound of claim 1, wherein L is an unsubstituted or substituted lower alkylene group.

58. The compound of claim 57, wherein the lower alkylene group is ethylene, propylene, or butylene.

59. The compound of claim 1, wherein the compound of Formula (I) is selected from the group consisting of:

60. The compound of claim 1, wherein the compound is selected from the group consisting of:

61. The compound of claim 1, wherein the compound is selected from the group consisting of:

62. The compound of claim 1, wherein the compound is selected from the group consisting of:

63. The compound of claim 1, wherein the compound is selected from the group consisting of:

64. The compounds of claim 63, wherein the compounds have the following stereochemistry:

65. The compounds of claim 63, wherein the compound is selected from the group consisting of:

66. The compound of claim 1, wherein the compound is selected from the group consisting of:

67. The compound of claim 1, wherein the compound is selected from the group consisting of:

68. The compound of claim 1, wherein the compound is selected from the group consisting of:

69. The compound of claim 1, wherein the compound is selected from the group consisting of:

70. The compound of claim 1, wherein the compound is selected from the group consisting of:

71. The compound of claim 1, wherein the compound is selected from the group consisting of:

72. The compound of claim 1, wherein the compound is selected from the group consisting of:

73. The compound of claim 1, wherein the compound is selected from the group consisting of:

74. The compound of claim 1, wherein the compound is selected from the group consisting of:

75. The compound of claim 1, wherein the compound is selected from the group consisting of:

76. The compound of claim 1, wherein the compound is selected from the group consisting of:

77. The compound of claim 1, wherein the compound is selected from the group consisting of:

78. The compound of claim 1, wherein the compound is selected from the group consisting of:

79. The compound of claim 1, wherein the compound is selected from the group consisting of:

80. The compound of claim 1, wherein the compound is selected from the group consisting of:

81. The compound of claim 1, wherein the compound is selected from the group consisting of:

82. The compound of claim 1, wherein the compound is selected from the group consisting of:

83. The compounds of claim 82, wherein the compounds have the following stereochemistry:

84. The compound of claim 1, wherein the compound is selected from the group consisting of:

85. The compounds of claim 84, wherein the compounds have the following stereochemistry:

86. The compound of claim 1, wherein the compound is selected from the group consisting of:

87. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C001, C002, C003, C004, C005, C006, C007, C008, C009, C010, C011, C012, C013, C014, C015, C016, C017, C018, C019, C020, C021, C022, C023, C024, C025, C026, C027, C028, C029, C030, C031, C032, C033, C034, C035, C036, C037, C038, C039, C040, C041, C042, C043, C044, C045, C046, C047, C048, C049, and C050.

88. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C051, C052, C053, C054, C055, C056, C057, C058, C059, C060, C061, C062, C063, C064, C065, C066, C067, C068, C069, C070, C071, C072, C073, C074, C075, C076, C077, C078, C079, C080, C081, C082, C083, C084, C085, C086, C087, C088, C089, C090, C091, C092, C093, C094, C095, C096, C097, C098, C099, and C100.

89. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C101, C102, C103, C104, C105, C106, C107, C108, C109, C010, C111, C112, C113, C114, C115, C116, C117, C118, C119, C120, C121, C122, C123, C124, C125, C126, C127, C128, C129, C130, C131, C132, C133, C134, C135, C136, C137, C138, C139, C140, C141, C142, C143, C144, C145, C146, C147, C148, C149, and C150.

90. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C151, C152, C153, C154, C155, C156, C157, C158, C159, C160, C161, C162, C163, C164, C165, C166, C167, C168, C169, C170, C171, C172, C173, C174, C175, C176, C177, C178, C179, C180, C181, C182, C183, C184, C185, C186, C187, C188, C189, C190, C191, C192, C193, C194, C195, C196, C197, C198, C199, and C200.

91. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C201, C202, C203, C204, C205, C206, C207, C208, C209, C210, C211, C212, C213, C214, C215, C216, C217, C218, C219, C220, C221, C222, C223, C224, C225, C226, C227, C228, C229, C230, C231, C232, C233, C234, C235, C236, C237, C238, C239, C240, C241, C242, C243, C244, C245, C246, C247, C248, C249, and C250.

92. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C251, C252, C253, C254, C255, C256, C257, C258, C259, C260, C261, C262, C263, C264, C265, C266, C267, C268, C269, C270, C271, C272, C273, C274, C275, C276, C277, C278, C279, C280, C281, C282, C283, C284, C285, C286, C287, C288, C289, C290, C291, C292, C293, C294, C295, C296, C297, C298, C299, and C300.

93. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C301, C302, C303, C304, C305, C306, C307, C308, C309, C310, C311, C312, C313, C314, C315, C316, C317, C318, C319, C320, C321, C322, C323, C324, C325, C326, C327, C328, C329, C330, C331, C332, C333, C334, C335, C336, C337, C338, C339, C340, C341, C342, C343, C344, C345, C346, C347, C348, C349, and C350.

94. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C351, C352, C353, C354, C355, C356, C357, C358, C359, C360, C361, C362, C363, C364, C365, C366, C367, C368, C369, C370, C371, C372, C373, C374, C375, C376, C377, C378, C379, C380, C381, C382, C383, C384, C385, C386, C387, C388, C389, C390, C391, C392, C393, C394, C395, C396, C397, C398, C399, and C400.

95. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C401, C402, C403, C404, C405, C406, C407, C408, C409, C410, C411, C412, C413, C414, C415, C416, C417, C418, C419, C420, C421, C422, C423, C424, C425, C426, C427, C428, C429, C430, C431, C432, C433, C434, C435, C436, C437, C438, C439, C440, C441, C442, C443, C444, C445, C446, C447, C448, C449, and C450.

96. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C451, C452, C453, C454, C455, C456, C457, C458, C459, C460, C461, C462, C463, C464, C465, C466, C467, C468, C469, C470, C471, C472, C473, C474, C475, C476, C477, C478, C479, C480, C481, C482, C483, C484, C485, C486, C487, C488, C489, C490, C491, C492, C493, C494, C495, C496, C497, C498, C499, and C500.

97. The compound of claim 1 wherein the compound is selected from the group consisting of a compound identified as C501, C502, C503, C504, C505, C506, C507, C508, C509, C510, C511, C512, C513, C514, C515, C516, C517, C518, C519, C520, C521, C522, C523, C524, C525, C526, C527, C528, C529, C530, C531, C532, C533, C534, C535, C536, C537, C538, C539, C540, C541, C542, C543, C544, C545, C546, C547, C548, C549, and C550.

98. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C551, C552, C553, C554, C555, C556, C557, C558, C559, C560, C561, C562, C563, C564, C565, C566, C567, C568, C569, C570, C571, C573, C574, C575, C576, C577, C57$, C579, C580, C581, C582, C583, C584, C585, C586, C587, C588, C589, C590, C591, C592, C593, C594, C595, C596, C597, C598, C599, and C600.

99. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C601, C602, C603, C604, C605, C606, C607, C608, C609, C610, C611, C612, C613, C614, C615, C616, C617, C618, C619, C620, C621, C622, C623, C624, C625, C626, C627, C628, C629, C630, C631, C632, C633, C634, C635, C636, C637, C638, C639, C640, C641, C642, C643, C644, C645, C646, C647, C648, C649, and C650.

100. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C651, C652, C653, C654, C655, C656, C657, C658, C659, C660, C661, C662, C663, C664, C665, C666, C667, C668, C669, C670, C671, C672, C673, C674, C675, C676, C677, C678, C679, C680, C681, C682, C683, C684, C685, C686, C687, C688, C689, C690, C691, C692, C693, C694, C695, C696, C697, C698, C699, and C700.

101. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C701, C702, C703, C704, C705, C706, C707, C708, C709, C710, C711, C712, C713, C714, C715, C716, C717, C718, C719, C720, C721, C722, C723, C724, C725, C726, C727, C728, C729, C730, C731, C732, C733, C734, C735, C736, C737, C738, C739, C740, C741, C742, C743, C744, C745, C746, C747, C748, C749, and C750.

102. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C751, C752, C753, C754, C755, C756, C757, C758, C759, C760, C761, C762, C763, C764, C765, C766, C767, C768, C769, C770, C771, C772, C773, C774, C775, C776, C777, C778, C779, C780, C781, C782, C783, C784, C785, C786, C787, C788, C789, C790, C791, C792, C793, C794, C795, C796, C797, C798, C799, and C800.

103. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C801, C802, C803, C804, C805, C806, C807, C808, C809, C810, C811, C812, C813, C814, C815, C816, C817, C818, C819, C820, C821, C822, C823, C824, C825, C826, C827, C828, C829, C830, C831, C832, C833, C834, C835, C836, C837, C838, C839, C840, C841, C842, C843, C901, C902, C903, C904, and C905.

104. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C844, C845, C846, C847, C848, C849, C850, C851, C852, C853, C854, C855, C856, C857, C858, C859, C860, C861, C862, C863, C864, C865, C866, C867, C868, C869, C870, C871, C872, C873, C874, C875, C876, C877, C878, C879,

105. The compound of claim 1, wherein the compound is selected from the group consisting of a compound identified as C880, C881, C882, C883, C884, C885, C886, C887, C888, C889, C890, C891, C892, C893, C894, C895, C896, C897, C898, C899,

106. A pharmaceutical composition, comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier, excipient, or diluent.

107. A method of treating or preventing a disorder or condition selected from the group consisting of obesity, an obesity-associated disorder, a metabolic disorder, metabolic syndrome, an endocrine disorder, an appetite disorder, an eating disorder, an eating disorder requiring appetite control, atherosclerosis, diabetes, diabetes mellitus, high cholesterol, hyperlipidemia, cachexia, anorexia, bulimia, inflammation, a chronic inflammatory disorder, rheumatoid arthritis, asthma, psoriasis, a cardiovascular disorder, angina, cardiac ischemia, cardiac failure, heart disease, congestive heart failure, ischemic heart disease, chronic heart disease, hemorrhagic shock, septic shock, cirrhosis, a neurological disorder, anxiety, depression, an attention deficit disorder, a memory disorder, a cognitive disorder, a gastrointestinal disorder, reduced gastric motility, reduced gastric and intestinal motility, excessive gastric motility, post-operative gastric ileus, delayed gastric emptying, delayed gastric emptying due to diabetes, delayed gastric emptying post-operatively, short bowel syndrome, a gastric ulcer, nausea, emesis, diarrhea, gastroparesis, diabetic gastroparesis, opioid-induced bowel dysfunction, chronic intestinal pseudoobstruction, a sleep disorder, insomnia, a hyperproliferative disorder, cancer, cancer cachexia, dwarfism, osteoporosis, a catabolic state, somatopause, osteopenia, a disorder of the pancreas, a hormone deficiency, gastrointestinal dumping syndrome, postgastroenterectomy syndrome, celiac disease, AIDS, wasting, age-related decline in body composition, hypertension, retinopathy, dyslipidemia, a gall stone, osteoarthritis, congestive heart failure, insulin resistance, burn, wound, protein loss, sexual dysfunction, a central nervous system disorder, a genetic disorder, irritable bowel syndrome (IBS), non-ulcer dyspepsia, Crohn'"'"'s disease, a gastroesophogeal reflux disorder, constipation, ulcerative colitis, pancreatitis, infantile hypertrophic pyloric stenosis, carcinoid syndrome, malabsorption syndrome, atrophic colitis, gastritis, gastric stasis, frailty, acromegaly, and protein loss comprising administering to a subject a pharmaceutically effective amount of a compound of claim 1.

108. The method of claim 107, wherein said compound alleviates or treats a disorder or condition by modulating, agonizing, inverse agonizing, or antagonizing a ghrelin receptor.

109. The method of claim 107, wherein said compound alleviates or treats a disorder or condition by inverse agonizing or antagonizing a ghrelin receptor.

110. The method of claim 107, wherein the disorder or condition is a disorder selected from the group consisting of a neurological disorder, anxiety, depression, an attention deficit disorder, a memory disorder, and a cognitive disorder.

111. The method of claim 107, wherein the disorder or condition is selected from the group consisting of obesity, metabolic syndrome, an appetite disorder, an eating disorder, an eating disorder requiring appetite control, atherosclerosis, diabetes, heart disease, high cholesterol, hyperlipidemia, cachexia, anorexia, and bulimia.

112. The method of claim 107, wherein the disorder or condition is a sleep disorder.

113. The method of claim 112, wherein the sleep disorder is insomnia or narcolepsy.

114. The method of claim 107, wherein the disorder or condition is selected from the group consisting of a reduced gastric motility, reduced gastric and intestinal motility, excessive gastric motility, post-operative gastric ileus, delayed gastric emptying, delayed gastric emptying due to diabetes, delayed gastric emptying post-operatively, short bowel syndrome, a gastric ulcer, nausea, emesis, diarrhea and a gastrointestinal disorder.

115. The method of claim 107, wherein the inflammation is caused by a disorder or condition selected from the group consisting of a chronic inflammatory disorder, rheumatoid arthritis, asthma, an allergy, and psoriasis.

116. The method of claim 107, wherein the disorder or condition is selected from the group consisting of a cardiovascular disorder, angina, cardiac ischemia, cardiac failure, heart disease, hemorrhagic shock, septic shock, and cirrhosis.

117. The method of claim 107, wherein the disorder or condition is selected from the group consisting of dwarfism, osteoporosis, a catabolic state, somatopause, and osteopenia.

118. The method of claim 107, wherein the disorder or condition is a hyperproliferative disorder or cancer.

119. The method of claim 107, wherein the disorder or condition is a disorder of the pancreas.

120. The method of claim 107, wherein the disorder or condition is a hormone deficiency.

121. A method of treating or alleviating obesity comprising administering to a subject a therapeutically effective amount of a compound of claim 1.

122. A method of alleviating or controlling a symptom associated with an eating disorder comprising administering to a subject a therapeutically effective amount of a compound of claim 1.

123. The method of claim 122, wherein the symptom is increased appetite or binge eating.

124. A method of promoting weight loss in a subject comprising administering to the subject a therapeutically effective amount of a compound of claim 1.

125. A method of preventing weight gain in a subject comprising administering to a subject a therapeutically effective amount of a compound of claim 1.

126. The method of claim 125, wherein the subject is taking a medication selected from the group consisting of insulin, thiazolidinedione, sulfonylurea, corticosteroid, progestational steroid, antihistamine, alpha-adrenergic blocker, beta-adrenergic blocker, an antidepressant, antipsychotic, and anticonvulsant.

127. A method of preventing weight loss in a subject comprising administering to a subject a therapeutically effective amount of a compound of claim 1.

128. The method of claim 127, wherein the weight loss is caused by chemotherapy, radiation therapy, temporary immobilization, permanent immobilization or dialysis.

129. A method for maintaining the weight of a subject comprising administering a therapeutically effective amount of a compound of claim 1.

130. A method of improving sleep architecture, facilitating induction of sleep, or improving the quality of sleep of a subject comprising administering to the subject a therapeutically effective amount of a compound of claim 1.

131. The method of claim 130, further comprising a sleep agent.

132. A method for maintaining the sleep of a subject comprising administering a therapeutically effective amount of a compound of claim 1.

133. The method of claim 132, further comprising a sleep agent.

134. A method for facilitating alertness or awakefulness of a subject comprising administering a therapeutically effective amount of a compound of claim 1.

135. The method of claim 134, wherein the subject is taking an agent that causes drowsiness or induces sleep.

136. A method of controlling the level of glucose in a subject comprising administering to the subject a therapeutically effective amount of a compound of claim 1.

137. A method of treating cancer comprising administering to a subject a therapeutically effective amount of a compound of claim 1.

138. A method of treating diabetes comprising administering to a subject a therapeutically effective amount of a compound of claim 1.

139. A method of preventing or alleviating inflammation comprising administering to a subject a therapeutically effective amount of a compound of claim 1.

140. The method of claim 139, wherein the inflammation is caused by a chronic inflammatory disease, rheumatoid arthritis, asthma, an allergy, or psoriasis.

141. A method of diagnosing a hormone deficiency comprising administering to a subject a therapeutically effective amount of a compound of claim 1.

142. A method of modulating production of a hormone comprising administering to a subject a therapeutically effective amount of a compound of claim 1.

143. A method of improving the memory of a subject comprising administering to the subject a therapeutically effective amount of a compound of claim 1.

144. A method of alleviating or treating a symptom associated with a neurological disorder comprising administering to a subject with altered cognition a therapeutically effective amount of a compound of claim 1.

145. A method for treating post-operative ileus or cachexia comprising administering to a subject with altered cognition a therapeutically effective amount of a compound of claim 1.

146. The method of claim 145, wherein the post-operative ileus or cachexia is caused by cancer, AIDS, a cardiac disease, a renal disease, or gastroparesis.

147. A method of modulating, agonizing, inverse agonizing, or antagonizing a ghrelin receptor comprising administering to a subject a therapeutically effective amount of a compound of claim 1.