Claims
- 1. A compound of Formula I or a pharmaceutically acceptable salt thereof, with Formula I being: ##STR87## wherein R.sub.1 and R.sub.2 are independently selected from H, halogen, CF.sub.3, or C.sub.1-4 alkoxy groups except that R.sub.1 and R.sub.2 cannot both be H simultaneously, or R.sub.1 and R.sub.2, when on adjacent carbon atoms, can be taken together to form a ##STR88## bridge with n being an integer from 1 to 3; R.sub.3 is H or C.sub.1-4 alkyl;
- R.sub.4 and R.sub.5 are each independently selected from H, C.sub.1-4 alkyl or phenyl;
- Y is N; and
- Ar is an unsubstituted phenyl ring; a substituted phenyl ring of structure II: ##STR89## wherein X.sub.p and X.sub.q may be halogen, nitro, amino, carboxamido, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkyl, C.sub.1-4 alkylthio or X.sub.p and X.sub.q can be taken together to form a ##STR90## bridge (n=1-3); or a heteroaryl group selected from 3-pyridinyl, 4-pyridinyl, 2-thienyl, 2-furanyl, and 1-methyl-2-pyrrolyl moieties.
- 2. The compound of claim 1 wherein R.sub.1 and R.sub.2 taken together form the bridge ##STR91## (n=1-3).
- 3. The compound of claim 2 wherein each of R.sub.3, R.sub.4 and R.sub.5 is H.
- 4. The compound of claim 1, Z-1-(4-fluorophenyl)-4-[4-(2,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol.
- 5. The compound of claim 1, Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol.
- 6. The compound of claim 1, Z-1-(4-fluorophenyl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol.
- 7. The compound of claim 1 wherein the compound is selected from the group consisting of:
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(phenylmethyl)-1-piperazinyl)cyclohexanol;
- Z-1-(4-methoxyphenyl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-[4-(1,3-benzodioxol-5-yl)-4-methoxycyclohexyl]-4-(phenylmethyl)piperazine;
- Z-1-(1,4-benzodioxan-6-yl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(3-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(3-fluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-fluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-methylphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-nitrophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-chlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-dichlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(4-fluorophenyl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;and
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-bromophenyl)methyl]-1-piperazinyl]cyclohexanol.
- 8. The compound of claim 1 wherein the compound is selected from the group consisting of:
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(phenylmethyl)-1-piperazinyl)cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-dichlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,3-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(3,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-iodophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(1,3-benzodioxol-4-yl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[2-fluoro-5-methoxyphenyl)-methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-bromophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(diphenylmethyl)-1-piperazinyl]cyclohexanol; and
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(1-phenylethyl)-1-piperazinyl]cyclohexanol.
- 9. The compound of claim 1 wherein the compound is selected from the group consisting of:
- Z-1-(4-fluorophenyl)-4-[4-[(3-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(4-fluorophenyl)-4-[4-[(2-chlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(4-fluorophenyl)-4-[4-[(2,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(4-fluorophenyl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol; and
- Z-1-[4-(4-fluorophenyl)-4-methoxy-1-cyclohexyl]-4-[(3-methoxyphenyl)methyl]piperazine.
- 10. The compound according to claim 1 selected from the group consisting of:
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-(4-methoxyphenyl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-[4-(1,3-benzodioxol-5-yl)-4-[4-(methoxycyclohexyl]-4-(phenylmethyl)piperazine;
- Z-1-(1,4-benzodioxan-6-yl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-(4-fluorophenyl)-4-[4-[(2,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol; and
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(2-bromophenyl)methyl]-1-piperazinyl]cyclohexanol.
- 11. A pharmaceutical composition comprising an effective anxiolytic amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 12. The composition of claim 11 wherein the compound is selected from the group consisting of:
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(phenylmethyl)-1-piperazinyl)cyclohexanol;
- Z-1-(4-methoxyphenyl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-[4-(1,3-benzodioxol-5-yl)-4-methoxycyclohexyl]-4-(phenylmethyl)piperazine;
- Z-1-(1,4-benzodioxan-6-yl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(3-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(3-fluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-fluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-methylphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-nitrophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(2-thienylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-chlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-dichlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(4-fluorophenyl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol; and
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-bromophenyl)methyl]-1-piperazinyl]cyclohexanol.
- 13. A method of treating anxiety comprising administering to a patient in need thereof an effective amount of a compound of claim 1.
- 14. The method of claim 13 wherein the compound is Z-1-(4-fluorophenyl)-4-[4-(2,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol.
- 15. The method of claim 13 wherein the compound is selected from the group consisting of:
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(phenylmethyl)-1-piperazinyl)cyclohexanol;
- Z-1-(4-methoxyphenyl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-[4-(1,3-benzodioxol-5-yl)-4-methoxycyclohexyl]-4-(phenylmethyl)piperazine;
- Z-1-(1,4-benzodioxan-6-yl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxan-5-yl)-4-[4-[(3-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(3-fluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-fluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-methylphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-nitrophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(2-thienylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-chlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-dichlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(4-fluorophenyl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol; and
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-bromophenyl)methyl]-1-piperazinyl]cyclohexanol.
- 16. The method of claim 13 wherein the compound is selected from the group consisting of:
- Z-1-(1,3-benzodioxol-5-yl)-4[4-(phenylmethyl)-1-piperazinyl)cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-dichlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,3-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(3,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-iodophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(1,3-benzodioxol-4-yl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-bromophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(diphenylmethyl)-1-piperazinyl]cyclohexanol; and
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(1-phenylethyl)-1-piperazinyl]cyclohexanol.
- 17. The method of claim 13 wherein the compound is selected from the group consisting of:
- Z-1-(4-fluorophenyl)-4-[4-[(3-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(4-fluorophenyl)-4-[4-[(2-chlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(4-fluorophenyl)-4-[4-[(2,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(4-fluorophenyl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol; and
- Z-1-[4-(4-fluorophenyl)-4-methoxy-1-cyclohexyl]-4-[(3-methoxyphenyl)-methyl]piperazine.
- 18. The method of claim 13 wherein the compound is Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol.
- 19. The method of claim 13 wherein the compound is Z-1-(4-fluorophenyl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol.
- 20. A method for the prophylactic treatment of migraines comprising administering to a patient in need thereof an effective amount of a compound of claim 1.
- 21. The method of claim 20 wherein the compound is selected from the group consisting of:
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-(4-methoxyphenyl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-[4-(1,3-benzodioxol-5-yl)-4-methoxycyclohexyl]-4-(phenylmethyl)piperazine;
- Z-1-(1,4-benzodioxan-6-yl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(3-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(3-fluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-fluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-methyophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-nitrophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-chlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-dichlorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2,5-difluorophenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol;
- Z-1-(4-fluorophenyl)-4-[4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperazinyl]cyclohexanol; and
- Z-1-(1,3-benzodioxol-5-yl)-4-[4-[(2-bromophenyl)methyl]-1-piperazinyl]cyclohexanol.
CROSS REFERENCE TO RELATED PATENT
This application is a divisional application of Ser. No. 08/198,165, filed on Feb. 17, 1994, now U.S. Pat. No. 5,387,593, which was a continuation-in-part of Ser. No. 07/952,229, filed Sep. 28, 1992 and now abandoned, which was a continuation-in-part of Ser. No. 07/806,989 filed Dec. 13, 1991 and now abandoned.
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Divisions (1)
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Number |
Date |
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198165 |
Feb 1994 |
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Continuation in Parts (2)
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952229 |
Sep 1992 |
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Parent |
806989 |
Dec 1991 |
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