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):	Catt; John D. (Southington, CT), Johnson; Graham (Madison, CT), Keavy; Daniel J. (Killingworth, CT), Mattson; Ronald J. (Meriden, CT), Parker; Michael F. (Middletown, CT), Takaki; Katherine S. (Middletown, CT), Yevich; Joseph P. (Southington, CT)
Assignee:	Bristol-Myers Squibb Company (Princeton, NJ)
Application Number:	08/987,478
Patent Claims:	1. A compound of Formula I or a pharmaceutically acceptable solvate thereof having the Formula: ##STR28## wherein Q.sup.1 and Q.sup.2 each are independently hydrogen or halogen; Y is CR.sup.3, CR.sup.3 R.sup.4 or (CH.sub.2).sub.n, with n=1; Z is oxygen and X is CH.sub.2 or CH; or X is oxygen and Z is CH.sub.2 or CH; R is hydrogen, halogen or C.sub.1-4 alkyl in both cases; m is 1 or 2; R.sup.1 is C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.1-3 haloalkyl, C.sub.1-6 alkylamino, C.sub.2-6 alkenyl, C.sub.1-4 alkoxy(C.sub.1-4)alkyl, C.sub.1-4 alkylthio(C.sub.1-4)alkyl or C.sub.1-4 trifluoromethylalkyl; R.sup.2 is hydrogen or C.sub.1-4 alkyl; and R.sup.3 and R.sup.4 each are independently hydrogen or C.sub.1-4 alkyl. 2. The compound of claim 1 wherein Q.sup.1 and Q.sup.2 are independently hydrogen or iodo and m is 1. 3. The compound of claim 2 wherein R.sup.1 is C.sub.1-6 alkyl, C.sub.3-4 cycloalkyl, C.sub.1-3 haloalkyl, C.sub.2-3 alkenyl, C.sub.1-2 alkoxy(C.sub.1-2)alkyl or C.sub.1-2 trifluoromethylalkyl and R.sup.2 is hydrogen. 4. The compound of claim 3 wherein X is CH.sub.2 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]acetami de; (-)-(trans)-N-[[2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methyl]butanam ide; (-)-(trans)-N-[[2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methyl]methoxy acetamide; (-)-(trans)-N-[[2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methyl]cyclopr opanecarboxamide; (-)-(trans)-N-[[2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methyl]trifluo roacetamide; (trans)-N-[[2-(2,3-dihydro-2,2-dimethyl-benzofuran-4-yl)cycloprop-1-yl]meth yl]propanamide; (trans)-N-[[2-(2,3-dihydro-2,2-dimethyl-benzofuran-4-yl)cycloprop-1-yl]meth yl]butanamide; (+)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]acetamide; (+)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]propanamide; (+)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]butanamide; (+)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]cyclopropane carboxamide; (+)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]-2-methylpropanamide; (+)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]chloroacetamide; (-)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]propanamide; (-)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]-2-me thyl]propanamide; (-)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]acetamide; (-)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]methoxyacetamide; (-)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]cyclopropane carboxamide; (-)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]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]propana mide; (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]pro panamide; (trans)-N-[[2-(2,3-dihydro-5-iodobenzofuran-4-yl)cyclopropyl]methyl]propana mide. 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]acetami de; (-)-(trans)-N-[[2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methyl]butanam ide; (-)-(trans)-N-[[2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methyl]cyclopr opanecarboxamide (+)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]acetamide; (+)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]propanamide; (+)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]butanamide; (+)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]cyclopropane carboxamide; (+)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]chloroacetamide; (-)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]propanamide; (-)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]acetamide; (-)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]cyclopropane carboxamide; (-)-(trans)-N-[[2-(2-methyl-2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methy l]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]propana mide; (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]pro panamide; and (trans)-N-[[2-(2,3-dihydro-5-iodobenzofuran-4-yl)cyclopropyl]methyl]propana mide. 7. The compound of claim 6, which is (trans)-N-[[2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methyl]propanamid e. 8. The compound of claim 6, which is (-)-(trans)-N-[[2-(2,3-dihydrobenzofuran-4-yl)cycloprop-1-yl]methyl]propan amide. 9. The compound of claim 3 wherein X is CH, Y is CR.sup.3 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.