Claims
- 1. (Cancel)
- 2. A pharmaceutical composition for treating or preventing a disease or condition in a mammal, the treatment or prevention of which can be effected or facilitated by altering dopamine mediated neurotransmission in said mammal, comprising an amount effective for treating or preventing such disease and condition of a compound of the formula I
- 3. The pharmaceutical composition according to claim 2 wherein Ar is phenyl, naphthyl, benzoxazolonyl, indolyl, indolonyl, benzimidazolyl, or quinolyl;
Ar1 is phenyl, pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl; A is O, S, SO2, CHOH or CH2; n is 0 or 1; and wherein Ar and Ar1 are independently and optionally substituted with up to three substiuents independently selected from the group consisting of fluoro, chloro, nitro, cyano, —NR1R2, —(C1-C6)alkoxy, COOR, —CONR1R2, and —(C1-C6)alkyl.
- 4. The pharmaceutical composition according to claim 3 wherein A is O, S or CH2.
- 5. The pharmaceutical composition according to claim 3 wherein Ar is optionally substituted phenyl; Ar1 is optionally substituted and is selected from the group consisting of phenyl, pyridinyl, and pyrimidinyl; A is 0 and n is 1.
- 6. The pharmaceutical composition according to claim 5 wherein A is 0, n is 1, Ar1 is 5-fluoropyrimidin-2-yl and Ar is optionally substituted phenyl, provided it is not p-fluorophenyl.
- 7. The pharmaceutical composition according to claim 2 wherein A is O or S, n is 1 and Ar is phenyl or substituted phenyl.
- 8. The pharmaceutical composition according to claim 5 wherein Ar1 is 5-fluoropyrimidin-2-yl or pyrimidin-2-yl.
- 9. The pharmaceutical composition according to claim 8 wherein Ar1 is 5-fluoro-pyrimidin-2-yl.
- 10. The pharmaceutical composition according to claim 2 wherein the compound is
(7S,9aS)-7-((3-Methyl-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; (7S,9aS)-7-(3-carbomethoxy-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; (7S,9aS)-7-(3-nitro-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; (7S,9aS)-7-(3-cyano-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; (7S,9aS)-7-(3-methoxy-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; (7S,9aS)-7-(3-acetamido-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; or (7S,9aS)-7-(3-(1,1-dimethyl)ethyl-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; and pharmaceutically acceptable salt thereof.
- 11. The pharmaceutical composition according to claim 2 wherein the serotonin reuptake inhibitor is setraline, fluroxetine, fenifluramine or fluoroxamine.
- 12. A pharmaceutical composition for treating or preventing or disease or condition in a mammal, the treatment or prevention of which can be effected or facilitated by altering dopamine mediated neurotransmission in said mammal comprising an amount effective for treating such disease and condition of a compounds of the formula
- 13. The pharmaceutical composition according to claim 12 wherein Ar is phenyl, naphthyl, benzoxazolonyl, indolyl, indolonyl, benzimidazolyl, or quinolyl;
Ar1 is phenyl, pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl; A is O, S, SO2, CHOH or CH2; n is 0 or 1; and wherein Ar and Ar1 are independently and optionally substituted with up to three substituents independently selected from the group consisting of fluoro, chloro, nitro, cyano, —NR1R2, —(C1-C6)alkoxy, COOR, —CONR1R2, and —(C1-C6)alkyl.
- 14. The pharmaceutical composition according to claim 13 wherein A is O, S or CH2.
- 15. The pharmaceutical composition according to claim 13 wherein Ar is optionally substituted phenyl; Ar1 is optionally substituted and is selected from the group consisting of phenyl, pyridinyl, and pyrimidinyl; A is 0 and n is 1.
- 16. The pharmaceutical composition according to claim 15 wherein A is 0, n is 1, Ar1 is 5-fluoropyrimidin-2-yl and Ar is optionally substituted phenyl, provided it is not p-fluorophenyl.
- 17. The pharmaceutical composition according to claim 12 wherein A is O or S, n is 1 and Ar is phenyl or substituted phenyl.
- 18. The pharmaceutical composition according to claim 15 wherein Ar1 is 5-fluoropyrimidin-2-yl or pyrimidin-2-yl.
- 19. The pharmaceutical composition according to claim 15 wherein Ar1 is 5-fluoro-pyrimidin-2-yl.
- 20. The pharmaceutical composition according to claim 12 wherein the compound is
(7S,9aS)-7-((3-Methyl-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; (7S,9aS)-7-(3-carbomethoxy-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; (7S,9aS)-7-(3-nitro-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; (7S,9aS)-7-(3-cyano-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; (7S,9aS)-7-(3-methoxy-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; (7S,9aS)-7-(3-acetamido-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; (7S,9aS)-7-(3-(1,1-dimethyl)ethyl-phenoxy)methyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine; and pharmaceutically acceptable salt thereof.
- 21. The pharmaceutical composition according to claim 12 wherein the serotonin-2 receptor antagonist is ketanserin, pelanserin, pipamperone, spiperone, pireneperin, or ritanserin.
- 22. The pharmaceutical composition according to claim 12 wherein the serotonin-2 receptor antagonist is of the formula
Parent Case Info
[0001] This application is a continuation under 35 U.S.C 120 of U.S. application Ser. No. 09/784,567, filed Mar. 15, 2001 which is a continuation of U.S. application Ser. No. 09/368,984, filed Aug. 5, 1999, which is a continuation-in-part of co-pending U.S. application Ser. No. 09/135,946, filed Aug. 18, 1998, now abandoned, which was a continuation-in-part of Ser. No. 08/809,145, filed Mar. 26, 1997, the national stage of International Application PCT/IB95/00689, filed Aug. 24, 1995, now U.S. Pat. No. 5,852,031, issued Dec. 22, 1998. PCT/IB95/00689 was a continuation of U.S. application Ser. No. 08/315,470, filed Sept. 30, 1994, now abandoned.
[0002] Compounds of this invention have affinity for serotonin (5HT) receptors, especially the serotonin 1a receptor (5HT1A), and are therefore useful for treatment of diseases or conditions which are caused by disorders of the serotonin system.
Continuations (4)
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Number |
Date |
Country |
Parent |
10213604 |
Aug 2002 |
US |
Child |
10852611 |
May 2004 |
US |
Parent |
09784567 |
Feb 2001 |
US |
Child |
10213604 |
Aug 2002 |
US |
Parent |
09368984 |
Aug 1999 |
US |
Child |
09784567 |
Feb 2001 |
US |
Parent |
08315470 |
Sep 1994 |
US |
Child |
08809145 |
Mar 1997 |
US |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
09135946 |
Aug 1998 |
US |
Child |
09368984 |
Aug 1999 |
US |
Parent |
08809145 |
Mar 1997 |
US |
Child |
09135946 |
Aug 1998 |
US |