Substituted 9H-pyridino[2,3-b] indole and 9H-pyrimidino[4,5-b] indole derivatives: selective neuropeptide Y receptor ligands

09841550

09/841550

April 23, 2001

Disclosed are compounds of the formula: [chemical expression included] wherein Ar, R1, W and X are substituents as defined herein, which compounds are effective neuropeptide Y1 receptor antagonists, and are therefore useful in the treatment of a wide variety of clinical conditions which are characterized by the presence of an excess of neuropeptide Y.

Darrow, James (Wallingford, CT, US)

Neurogen Corporation, Steven J. Sarussi (Chicago, IL, US)

What is claimed is: 1. A compound of the formula: [chemical expression included] or pharmaceutically acceptable salts thereof wherein: Ar is phenyl, 1- or 2-naphthyl, 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, each of which is optionally mono-, di-, or trisubstituted with halogen, trifluoromethyl, hydroxy, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C3-C7 cycloalkylamino, carboxamido, C1-C6 alkylcarboxamido, C3-C7 cycloalkylcarboxamido, C1-C6 alkyl, (C3-C7 cycloalkyl) C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 alkoxy, (C3-C7 cycloalkyl) C1-C6 alkoxy, C3-C7 cycloalkoxy, with the proviso that at least one of the positions ortho or para to the point of attachment of Ar to the tricyclic ring system is substituted; R1 is hydrogen, halogen, trifluoromethyl, C1-C6 alkyl, (C3-C7 cycloalkyl) C1-C6 alkyl, C3-C7 cycloalkyl, or (C1-C6 alkylene)-G1—R2 wherein G1 is oxygen or sulfur and R2 is hydrogen, C1-C6 alkyl, or C3-C7 cycloalkyl; W is N or C—R3, wherein R3 is hydrogen or C1-C6 alkyl; X is [chemical expression included] wherein A1 is NR4R5 wherein R4 and R5 are independently hydrogen, a C1-C6 alkyl group which optionally forms a heterocycloalkyl group with Y, (C3-C7 cycloalkyl) C1-C6 alkyl, or C3-C7 cycloalkyl; C1-C6 alkanoyl, (C3-C7 cycloalkyl) C1-C6 alkanoyl, C3-C7 cycloalkanoyl, C1-C6 alkylsulfonyl, or C3-C7 cycloalkylsulfonyl with the proviso that R4 and R5 may not both be alkanoyl or alkylsulfonyl; C1-C6 heterocycloalkyl, wherein heterocycloalkyl is morpholinyl, piperazinyl, piperidinyl, or pyrrolidinyl; C1-C6 arylalkyl or C1-C6 heteroarylalkyl, where aryl is phenyl, and heteroaryl is 2-,3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 1-, 2- or 4-imidazolyl, 2-, 4-, or 5-oxazolyl, 2-, 4-, or 5-thiazolyl, 1-, 3- or 4-pyrazolyl, 1-, 3- or 4-triazolyl, 2-pyrazinyl, or 1-, 2- or 5-tetrazolyl, each of which is optionally mono-, di-, or tri-substituted with halogen, trifluoromethyl, hydroxy, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C3-C7 cycloalkylamino, C1-C6 alkylcarboxamido, C3-C7 cycloalkylcarboxamido, C1-C6 alkyl, (C3-C7 cycloalkyl) C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 alkoxy, (C3-C7 cycloalkyl) C1-C6 alkoxy, or C3-C7 cycloalkoxy, where any 2 adjacent substituents may together form a 5-7 fused cycloalkyl or heterocycloalkyl ring; NR4R5 taken together form a C3-C6 heterocycloalkyl, or a group of the formula: [chemical expression included] wherein e and f are independently 1, 2, or 3 and the sum of e and f is at least 3; and G2 is (i) NR6 wherein R6 is hydrogen, C1-C6 alkyl, (C3-C7 cycloalkyl) C1-C6 alkyl, or C3-C7 cycloalkyl; or (ii) CH(C0-C6 alkyl)-G3—R7 wherein G3 is —CONH—, —CONH(C1-C6 alkyl)-, —NH—, —NH(C1-C6 alkyl)-, —NH(C3-C7 cycloalkyl)-, and R7 is hydrogen, C1-C6 alkyl, (C3-C7 cycloalkyl) C1-C6 alkyl, or C3-C7 cycloalkyl; or (iii) —CONH2—, or —CO[N(C1-C6 alkylene)R8]— wherein R8 is hydrogen, C1-C6 alkyl, (C3-C7 cycloalkyl) C1-C6 alkyl, or C3-C7 cycloalkyl; A2 is NH, SO2, oxygen or sulfur; V is CH2, CO, CS, SO2, CH(C1-C6 alkyl), CH(C3-C7 cycloalkyl), with the proviso that V may not be CO, CS or SO2 when A2 is SO2, oxygen or sulfur; and Y is a bond or C1-C6 alkylene; or X is [chemical expression included] wherein heteroaryl is 2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 1-, 2- or 4-imidazolyl, 2-, 4-, or 5-oxazolyl, 1-, 3- , or 5-thiazolyl, 1-, 3- or 4-pyrazolyl, 1-, 3- or 4-triazolyl, 2-pyrazinyl, or 1-, 2- or 5-tetrazolyl, each of which is optionally mono- or di-substituted with halogen, trifluoromethyl, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C3-C7 cycloalkylamino, C1-C6 alkyl, (C3-C7 cycloalkyl) C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 alkoxy, or C3-C7 cycloalkoxy, with the proviso that tetrazolyl may have at most one substituent; Z is C1-C6 alkylene; and A2 is NH, SO2, oxygen or sulfur. 2. A compound according to claim 1 wherein W is CH or N, A2 is NH or O, and R1 is C1-C6 alkyl. 3. A compound according to claim 1 wherein W is CH or N, and wherein R4 and R5 are independently hydrogen, a C1-C6 alkyl group which optionally forms a heterocycloalkyl group with Y, (C3-C7 cycloalkyl) C1-C6 alkyl, or C3-C7 cycloalkyl. 4. A compound according to claim 4 wherein Ar is 2,4,6-trimethylphenyl, A2 is NH or O, Y is CH2, V is CH2 or (CH2)2, R4 ls hydrogen, and R5 is hydrogen, methyl, ethyl, propyl, isopropyl, 2-methylpropyl, 2-ethylpropyl, 1,1-dimethyl propyl, butyl, tert-butyl, 2-methylbutyl, 3-methylbutyl, 1,3-dimethyl butyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclopropylmethyl. 5. A compound according to claim 1 wherein W is CH or N, Ar is 2,4,6-trimethylphenyl, A2 is NH or O, Y is CH2, V is CH2 or (CH2)2, R4 is hydrogen, and R5 is C1-C6 heterocycloalkyl, wherein heterocycloalkyl is morpholin-4-yl, piperazin-4-yl, piperidin-4-yl, or pyrrolidin-2-yl. 6. A compound according to claim 1 wherein W is CH or N, Ar is 2,4,6-trimethylphenyl, A2 is NH or O, Y is CH2, V is CH2 or (CH2)2, and NR4R5 taken together form a C3-C6 heterocycloalkyl, or a group of the formula: [chemical expression included] wherein e and f are independently 1, 2, or 3 and the sum of e and f is at least 3; and G2 is (i) NR6 wherein R6 is hydrogen, C1-C6 alkyl, (C3-C7 cycloalkyl) C1-C6 alkyl, or C3-C7 cycloalkyl; or (ii) CH(C0-C6 alkyl)-G3—R7 wherein G3 is —CONH—, CONH(C1-C6 alkyl)-, —NH—, —NH(C1-C6 alkyl)-, —NH(C3-C7 cycloalkyl)-, and R7 is hydrogen, C1-C6 alkyl, (C3-C7 cycloalkyl) C1-C6 alkyl, C3-C7 cycloalkyl; or (iii) —CONH2—, or —CO[N(C1-C6 alkylene)R8]— wherein R8 is hydrogen, C1-C6 alkyl, (C3-C7 cycloalkyl) C1-C6 alkyl, or C3-C7 cycloalkyl. 7. A compound according to claim 6 wherein NR4R5 is pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, N-methylpiperazinyl. 8. A compound according to claim 1 wherein W is CH or N, and wherein R4 and R5 are independently hydrogen, C1-C6 arylalkyl or C1-C6 heteroarylalkyl, where aryl is phenyl, and heteroaryl is 2-,3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 1-, 2- or 4-imidazolyl, 2-, 4-, or 5-oxazolyl, 2-, 4-, or 5-thiazolyl, 1-, 3- or 4-pyrazolyl, 1-, 3- or 4-triazolyl, 2-pyrazinyl, or 1-, 2- or 5-tetrazolyl, each of which is optionally mono-, di-, or tri-substituted with halogen, trifluoromethyl, hydroxy, amino, C1-C6 alkylamino, C1-C6 dialkylamino, C3-C7 cycloalkylamino, C1-C6 alkylcarboxamido, C3-C7 cycloalkylcarboxamido, C1-C6 alkyl, (C3-C7 cycloalkyl) C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 alkoxy, (C3-C7 cycloalkyl) C1-C6 alkoxy, or C3-C7 cycloalkoxy, where any 2 adjacent substituents may together form a 5-7 fused cycloalkyl or heterocycloalkyl ring. 9. A compound according to claim 8 wherein Ar is 2,4,6-trimethylphenyl, A2 is NH or O, Y is CH2, V is CH2 or (CH2)2, R4 is hydrogen, and R5 is (CH2)2-phenyl, (CH2)3-phenyl, (CH2)4-phenyl, (CH2)2-(2-methoxy) phenyl, (CH2)2-(3-methoxy) phenyl, (CH2)2-(4-hydroxy) phenyl, (CH2)2-(4-methoxy) phenyl, (CH2)2-(4-ethoxy) phenyl, (CH2)2-(3-methoxy-4-ethoxy) phenyl, (CH2)2-(3-methoxy-4-isopropoxy) phenyl, (CH2)2-(3-methoxy-4-isobutyloxy) phenyl, (CH2)2-(3-methoxy-4-cyclopropylmethyloxy) phenyl, (CH2)2-(2,4-dimethoxy) phenyl, (CH2)2-(3,4-dimethoxy) phenyl, (CH2)2-(3-methoxy-4-hydroxy) phenyl, (CH2)2-(3-methoxy-4-propoxy)phenyl, (CH2)2-(3-methoxy-4-propoxy) phenyl, (CH2)2-(3-methoxy-4-butoxy) phenyl, (CH2)2-(3-methoxy-4-pentoxy)phenyl, (CH2)2-(3-methoxy-4-cyclopentyloxy) phenyl, (CH2)2-(3-methoxy-4-cyclohexyloxy) phenyl, (CH2)2-(2H-benzo[3,4-d]1,3-dioxolan-5-yl), (CH2)2-(2H,3H-benzo[e]1,4-dioxin-6-yl), (CH2)2-(4-trifluoromethyl) phenyl, (CH2)2-(4-amino) phenyl, or (CH2)2-(4-dimethylamino) phenyl. 10. A compound according to claim 8 wherein Ar is 2,4,6-trimethylphenyl, A2 is NH or O, Y is CH2, V is CH2 or (CH2)2, R4 is hydrogen, and R5 is (CH2)2-pyridin-2-yl, (CH2)2-pyridin-3-yl, (CH2)2-pyridin-4-yl, (CH2)2-(2-methyl-imidazol-4-yl), CH2-imidazol-5-yl, or (CH2)2-(imidazol-5-yl). 11. A compound according to claim 1, which is [2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl](2-(4-piperidyl) ethyl) amine. 12. A compound of the formula: [chemical expression included] where Rx and Ry are methyl; or NRxRy represents pyrrolidinyl. 13. A compound according to claim 1, which is [2-(1-ethylimidazol-5-yl)ethyl][2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino [4,5-b] indol-4-yl] amine. 14. A compound of the formula: [chemical expression included] where Rx is selected from 3,4-dimethoxybenzylcarbonyl; 4-methoxybenzylcarbonyl; imidazol-5-ylcarbonyl; pyrazin-2-ylcarbonyl; 2-(4-ethoxy-3-methoxyphenyl)ethyl; 2-(4-trifluoromethylphenyl)ethyl; 2-(4-ethoxyphenyl)ethyl; 2-(4-methoxyphenyl)ethyl; 2-(imidazol-5-yl)ethyl; 2-phenylethyl; imidazol-5-ylmethylcarbonyl; cyclopropylcarbonyl; cyclobutyl; 2-methylimidazol-4-ylmethyl; imidazol-5-ylmethyl; cyclohexyl; cyclopentyl; cyclopropyl; ethyl; isopropyl; methyl; propyl; 2-(morpholin-4-yl)ethyl; cycloheptyl; (2-methyl-(1,3-thiazol-4-yl)methyl; (5-bromo-2-methyl-(1,3-thiazol-4-yl)methyl; and (2H,3H-benzo[e]1,4-dioxin-6-yl). 15. A compound of the formula: [chemical expression included] where f is 3 and NRxRy represents piperidin-4-yl; f is 3, Rx is hydrogen, and Ry is 2-(morpholin-4-yl)ethyl; f is 3 and Rx and Ry are hydrogen; f is 3 and NRxRy represents pyrrolidinyl; or f is 4 and Rx and Ry are hydrogen. 16. A compound of the formula: [chemical expression included] where Rx is 1,1-dimethylpropyl; 1,3-dimethylbutyl; 2-ethylpropyl; 2-methylbutyl; 2-methylpropyl; 3-methylbutyl; 2-(2-methoxyphenyl)ethyl; 2-(2,4-dimethoxyphenyl)ethyl; 2-(3-methoxy-4-(cyclopropylmethoxy)phenyl)ethyl; 2-(3-methoxy-4-cyclohexyloxyphenyl)ethyl; 2-(3-methoxy-4-ethoxyphenyl)ethyl; 2-(3-methoxy-4-isopropoxyphenyl)ethyl; 2-(3-methoxy-4-butoxyphenyl)ethyl; 2-(3-methoxy-4-(2-methylpropoxy)phenyl)ethyl; 2-(3-methoxy-4-hydroxyphenyl)ethyl; 2-(3-methoxy-4-pentoxyphenyl)ethyl; 2-(3,4-dimethoxyphenyl)ethyl; 2-(4-ethoxyphenyl)ethyl; 2-(4-methoxyphenyl)ethyl; 2-(4-aminophenyl)ethyl; 2-(4-hydroxyphenyl)ethyl; 2-(imidazol-5-yl)ethyl; 2-(morpholin-4-yl)ethyl; 2-phenylethyl; 2-(2-pyridyl)ethyl; 2-(3-pyridyl)ethyl; 2-(4-pyridyl)ethyl; 3-phenylpropyl; 4-phenylbutyl; butyl; cyclobutyl; 3-methoxybenzyl; 4-ethoxybenzyl; 4-methoxybenzyl; cyclopropylmethyl; cyclohexyl; cyclopentyl; ethyl; hexyl; isopropyl; methyl; propyl; tert-butyl; 4-(dimethylamino)phenylmethyl; (2H,3H-benzo[e]1,4-dioxin-6-yl)carbonylmethyl; 2-((2H,3H-benzo[e]1,4-dioxin-6-yl)carbonyl)ethyl; or 2-(2H-benzo[3,4-d]1,3-dioxolan-5-yl)ethyl; cycloheptyl; 2-(3,4-dimethoxyphenyl)ethyl. 17. A compound according to claim 1, which is 4-(2-(2-(4-Methoxyphenyl)ethylamino)ethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyridino[2,3-b]indole. 18. A compound according to claim 1, which is 4-(2-Amino-2-methylethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyridino[2,3-b]indole. 19. A compound according to claim 1, which is 4-(2-Aminoethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyridino[2,3-b]indole. 20. A compound according to claim 1, which is 4-(2-Dimethylamino-1-oxoethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyridino[2,3-b]indole. 21. A compound according to claim 1, which is 4-(2-(1-Methyl-2-pyrrolidino)ethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyridino[2,3-b]indole. 22. A compound according to claim 1, which is 4-(2-Aminoethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyrimidino[4,5-b]indole. 23. A compound according to claim 1, which is 4-(2-(Cyclohexylamino)ethyl)oxy-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyrimidino[4,5-b]indole. 24. A compound according to claim 1, which is A compound according to claim 1, which is 4-(2-(Cyclohexylamino)ethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyrimidino[4,5-b]indole. 25. A compound according to claim 1, which is 4-(2-(2-Phenethylamino)ethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyrimidino[4,5-b]indole. 26. A compound according to claim 1, which is 2-(3,4-dimethoxyphenyl)-N-(2-{[2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amino}ethyl)acetamide. 27. A compound according to claim 1, which is (2-{[2-(3,4-dimethoxyphenyl)ethyl]amino}ethyl)[2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine. 28. A compound according to claim 1, which is 4-(N-(2-hydroxyethyl)-N-cyclopropylmethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyrimidino[4,5-b]indole. 29. A compound according to claim 1, which is 4-(2-(Cyclopropylmethylamino)ethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyrimidino[4,5-b]indole. 30. A compound according to claim 1, which is 4-(2-(1-Oxo-2-(3-methoxy-4-hydroxyphenyl)ethylamino) ethyl) amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyridino[2,3-b]indole. 31. A compound according to claim 1, which is 4-(2-(1-Oxo-2-(3-methoxy-4-propoxyphenyl)ethylamino) ethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyridino[2,3-b]indole. 32. A compound according to claim 1, which is 4-(2-(2-(3-Methoxy-4-propoxyphenyl) ethylamino) ethyl) amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyridino[2,3-b]indole. 33. A compound according to claim 1, which is 4-(2-(1-Oxo-2-(3-methoxy-4-cyclopentyloxyphenyl) ethylamino)ethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyridino[2,3-b]indole. 34. A compound according to claim 1, which is 4-(2-(2-(3-Methoxy-4-cyclopentyloxyphenyl)ethylamino)ethyl)amino-2-methyl-9-(2,4,6-trimethylphenyl)-9H-pyridino[2,3-b]indole. 35. A compound according to claim 1, which is (2-{[2-(3,4-dimethoxyphenyl)ethyl]amino}ethyl)[9-(2,6-dimethylphenyl)-2-methylpyridino[2,3-b]indol-4-yl]amine. 36. A compound according to claim 1, which is [9-(3,5-dimethylphenyl)-2-methylpyridino[2,3-b]indol-4-yl](2-{[2-(4-methoxyphenyl)ethyl]amino}ethyl)amine. 37. A compound according to claim 1, which is (cyclopropylmethyl){2-[2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yloxy]ethyl}amine. 38. A compound according to claim 1, which is [9-(3,5-dimethylphenyl)-2-methylpyridino[2,3-b]indol-4-yl][2-(cyclohexylamino)ethyl]amine. 39. A compound according to claim 1, which is [9-(2,4-dimethylphenyl)-2-methylpyridino[2,3-b]indol-4-yl][2-(cyclohexylamino)ethyl]amine. 40. A compound according to claim 1, which is [9-(3,5-dimethylphenyl)-2-methylpyridino[2,3-b]indol-4-yl][2-(cyclopentylamino)ethyl]amine. 41. A compound according to claim 1, which is [2-(cyclopentylamino)ethyl][2-ethyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine. 42. A compound according to claim 1, which is [9-(2,4-dimethylphenyl)-2-methylpyridino[2,3-b]indol-4-yl][2-(cyclopentylamino)ethyl]amine. 43. A compound according to claim 1, which is [2-(ethylamino)ethyl][9-(4-methoxy-2-methylphenyl)-2-methylpyrimidino[4,5-b]indol-4-yl]amine. 44. A compound according to claim 1, which is [9-(4-chloro-2-methylphenyl)-2-methylpyrimidino[4,5-b]indol-4-yl][2-(ethylamino)ethyl]amine. 45. A compound according to claim 1, which is (tert-butyl){2-[2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yloxy]ethyl}amine. 46. A compound according to claim 1, which is (2-aminoethyl)[2-ethyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine. 47. A compound according to claim 1, which is (2-aminoethyl)[2-(trifluoromethyl)-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine. 48. A compound according to claim 1, which is (2-aminoethyl) [9-(4-methoxy-2-methylphenyl)-2-methylpyrimidino[4,5-b]indol-4-yl]amine. 49. A compound according to claim 1, which is cyclopentylmethyl(2-{[2-methyl-9-(2,4,6-trimethylphenyl)pyridino[2,3-b]indol-4-yl]amino}ethyl)amine. 50. A compound according to claim 1, which is 2-methyl-4-(3-piperidylpropoxy)-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indole. 51. A compound according to claim 1, which is 2-{[2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amino}acetamide. 52. A compound according to claim 1, which is [((2S)pyrrolidin-2-yl)methyl][2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine. 53. A compound according to claim 1, which is [2-(cyclopentylamino)propyl][2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine. 54. A compound according to claim 1, which is (2-aminopropyl) [2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine. 55. A compound according to claim 1, which is (2-{[2-(4-ethoxy-3-methoxyphenyl)ethyl]amino}propyl)[2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine 56. A compound according to claim 1, which is [2-(cyclopentylamino)-2-methylpropyl][2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine. 57. A compound according to claim 1, which is [2-(cyclopropylamino)-2-methylpropyl][2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine. 58. A compound according to claim 1, which is (2-amino-2-methylpropyl)[2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine. 59. A compound according to claim 1, which is (cis-2-aminocyclohexyl)[2-methyl-9-(2,4,6-trimethylphenyl)pyrimidino[4,5-b]indol-4-yl]amine. 60. The use of a compound according to claim 1 for the manufacture of a pharmaceutical composition for the prophylaxis and treatment of diseases or disorders associated with an excess of neuropeptide Y. 61. A method of treating or preventing a physiological condition in a mammal characterized by the presence of an excess of neuropeptide Y which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a compound according to claim 1, a prodrug, or a pharmaceutically acceptable salt thereof. 62. A pharmaceutical composition according to claim 1 for the treatment of disorders or disease states caused by &eating disorders, of obesity, bulimia nervosa, diabetes, dislipidemia, hypertension, memory loss, epileptic seizures, migraine, sleep disorders, pain, sexual/reproductive disorders, depression, anxiety, cerebral hemorrhage, shock, congestive heart failure, nasal congestion or diarrhea.

256; 267; 292; 333; 250; 85

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