Details for Patent: 5,981,571
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Title: | Benzodioxa alkylene ethers as melatonergic agents |
Abstract: | Novel derivatives of benzodioxa alkylene ethers 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) |
Filing Date: | Oct 09, 1998 |
Application Number: | 09/169,784 |
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; X is oxygen; Y is (CH.sub.2).sub.n, with n=1-4; Z is oxygen; R is hydrogen, halogen or C.sub.1-4 alkyl in both cases; m is 1 or2; 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; and R.sup.2 is 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 oxygen, Y is (CH.sub.2)n in which n is 1or 2 and Z is oxygen. 5. The compound of claim 4, selected from the group consisting of: (trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl]acetamide; (-)-(trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl]acetamide; (trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl]propanamide; (-)-(trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl] propanamide; (trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl]butanamide; (-)-(trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl] butanamide; (trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl]cyclopropane carboxamide; (-)-(trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl] cyclopropane carboxamide; (trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl]-2-methylpropanam ide; (-)-(trans)-N-[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl]-2-methylpropa namide; (-)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]p ropanamide; (-)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]a cetamide; (-)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]c yclopropanecarboxamide; (-)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]b utanamide; (+)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]p ropenamide; (-)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]t rifluoroacetamide; (-)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl) cycloprop-1-yl]methyl]-3,3,3-trifluoropropanamide; (+)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]p ropanamide; (trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]-methyl]acet amide; (trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]-methyl]prop anamide; (trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]-methyl]buta namide; (trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]-2-me thylpropanamide; and (trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]-methyl]cycl opropane carboxamide. 6. The compound of claim 5, selected from the group consisting of: (trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl]acetamide; (-)-(trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl]acetamide; (trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl]propanamide; and (-)-(trans)-N-[[2-(1,3-benzodioxol-4-yl)cycloprop-1-yl]methyl] propanamide. 7. The compound of claim 5, selected from the group consisting of: (-)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]p ropanamide; (-)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]a cetamide; (-)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]c yclopropanecarboxamide; and (-)-(trans)-N-[[2-(2,3-dihydro-1,4-benzodioxin-5-yl)cycloprop-1-yl]methyl]b utanamide. 8. 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. 9. 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. 10. 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. 11. 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. |