Claims for Patent: 5,856,529

Summary for Patent: 5,856,529

Title:	Benzofuran and dihydrobenzofuran melatonergic agents
Abstract:	Novel derivatives of benzofuran and dihydrobenzofuran are provided which are useful as melatonergic agents.
Inventor(s):	John D. Catt, Graham Johnson, Daniel J. Keavy, Ronald J. Mattson, Michael F. Parker, Katherine S. Takaki, Joseph P. Yevich
Assignee:	Bristol Myers Squibb Co
Application Number:	US08/987,478
Patent Claims:	1. A compound of Formula I or a pharmaceutically acceptable solvate thereof having the Formula: ##STR28## wherein Q1 and Q2 each are independently hydrogen or halogen;Y is CR3, CR3 R4 or (CH2)n, with n=1; Z is oxygen and X is CH2 or CH; or X is oxygen and Z is CH2 or CH; R is hydrogen, halogen or C1-4 alkyl in both cases; m is 1 or 2; R1 is C1-6 alkyl, C3-6 cycloalkyl, C1-3 haloalkyl, C1-6 alkylamino, C2-6 alkenyl, C1-4 alkoxy(C1-4)alkyl, C1-4 alkylthio(C1-4)alkyl or C1-4 trifluoromethylalkyl; R2 is hydrogen or C1-4 alkyl; and R3 and R4 each are independently hydrogen or C1-4 alkyl. 2. The compound of claim 1 wherein Q1 and Q2 are independently hydrogen or iodo and m is 1. 3. The compound of claim 2 wherein R1 is C1-6 alkyl, C3-4 cycloalkyl, C1-3 haloalkyl, C2-3 alkenyl, C1-2 alkoxy(C1-2)alkyl or C1-2 trifluoromethylalkyl and R2 is hydrogen. 4. The compound of claim 3 wherein X is CH2 and Z is oxygen. 5. A compound of claim 4 selected from the group consisting of:(+)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (-)-(trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!acetamide; (-)-(trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!butanamide; (-)-(trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!methoxyacetamide; (-)-(trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!cyclopropanecarboxamide; (-)-(trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!trifluoroacetamide; (trans)-N- 2-(2,3-dihydro-2,2-dimethyl-benzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (trans)-N- 2-(2,3-dihydro-2,2-dimethyl-benzofuran-4-yl)cycloprop-1-yl!methyl!butanamide; (+)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!acetamide; (+)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (+)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!butanamide; (+)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!cyclopropane carboxamide; (+)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!-2-methylpropanamide; (+)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!chloroacetamide; (-)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (-)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!-2-methyl!propanamide; (-)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!acetamide; (-)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!methoxyacetamide; (-)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!cyclopropane carboxamide; (-)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!butanamide; (trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!acetamide; (-)-(trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide (trans)-N- 2-(2,3-dihydrobenzofuran-4-yl) cycloprop-1-yl!methyl!butanamide; (trans)-N- 2-(2,3-dihydro-5,7-diiodobenzofuran-4-yl)cyclopropyl!methyl!propanamide; (trans)-N- 2-(2,3-dihydro-5-iodobenzofuran-4-yl)cyclopropyl!methyl!propanamide. 6. The compound of claim 5, selected from the group consisting of:(+)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (-)-(trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!acetamide; (-)-(trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!butanamide; (-)-(trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!cyclopropanecarboxamide (+)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!acetamide; (+)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (+)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!butanamide; (+)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!cyclopropane carboxamide; (+)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!chloroacetamide; (-)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (-)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!acetamide; (-)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!cyclopropane carboxamide; (-)-(trans)-N- 2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!butanamide; (trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!acetamide; (-)-(trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!butanamide; (trans)-N- 2-(2,3-dihydro-5,7-diiodobenzofuran-4-yl)cyclopropyl!methyl!propanamide; and (trans)-N- 2-(2,3-dihydro-5-iodobenzofuran-4-yl)cyclopropyl!methyl!propanamide. 7. The compound of claim 6, which is (trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide. 8. The compound of claim 6, which is (-)-(trans)-N- 2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl!methyl!propanamide. 9. The compound of claim 3 wherein X is CH, Y is CR3 and Z is oxygen. 10. The compound of claim 9 selected from the group consisting of:(-)-(trans)-N- 2-(2-benzofuran-4-yl)cycloprop-1-yl!methyl!cyclopropane carboxamide; (-)-(trans)-N- 2-(benzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (trans)-N- 2-(2-methyl-benzofuran-4-yl)cycloprop-1-yl!methyl!acetamide; (trans)-N- 2-(2-methyl-benzofuran-4-yl)cycloprop-1-yl!methyl!-propanamide; (trans)-N- 2-(2-methyl-benzofuran-4-yl)cycloprop-1-yl!methyl!-butanamide; (trans)-N- 2-(benzofuran-4-yl)cycloprop-1-yl!methyl!acetamide; (trans)-N- 2-(benzofuran-4-yl)cycloprop-1-yl!methyl!propanamide; (trans)-N- 2-(benzofuran-4-yl)cycloprop-1-yl!methyl!butanamide; (trans)-N- 2-(benzofuran-4-yl)cycloprop-1-yl!methyl!-2-methylpropanamide; and (trans)-N- 2-(benzofuran-4-yl)cycloprop-1-yl!methyl!cyclopropane carboxamide. 11. The compound of claim 10 selected from the group consisting of:(trans)-N- 2-(2-methyl-benzofuran-4-yl)cycloprop-1-yl!methyl!acetamide; (trans)-N- 2-(2-methyl-benzofuran-4-yl)cycloprop-1-yl!methyl!-propanamide; (trans)-N- 2-(2-methyl-benzofuran-4-yl)cycloprop-1-yl!methyl!-butanamide; and (trans)-N- 2-(benzofuran-4-yl)cycloprop-1-yl!methyl!propanamide. 12. A method of treating sleep disorders in a patient in need of such treatment comprising administering to said patient a therapeutic amount of a compound of claim 1. 13. A composition useful for treating sleep disorders comprising a therapeutic amount of a compound of claim 1 and a suitable amount of a pharmaceutically acceptable carrier. 14. A method of treating circadian rhythm-related disorders in a patient in need of such treatment comprising administering to said patient a therapeutic amount of a compound of claim 1. 15. A composition useful for treating circadian rhythm-related disorders comprising a therapeutic amount of a compound of claim 1 and a suitable amount of a pharmaceutically acceptable carrier.