Claims
- 1. A compound of the formula: ##STR133## wherein X is --O--, --S--, --NH--, or --N(R.sub.2);
- R.sub.2 is selected from the group consisting of lower alkyl, aryl lower alkyl, aryl, cycloalkyl, aroyl, alkanoyl, and phenylsulfonyl groups;
- aryl is as defined hereinafter;
- p is 1 or 2;
- Y is hydrogen, lower alkyl, hydroxy, chlorine, fluorine, bromine, iodine, lower alkoxy, trifluoromethyl, nitro, or amino;
- R.sub.1 is --CR.sub.24 R.sub.27 --(CR.sub.23 R.sub.27).sub.n --, where n is 0, 1, 2 or 3; or
- --CHR.sub.24 CH.dbd.CH--CHR.sub.24 --,
- --CHR.sub.24 --C.dbd.C--CHR.sub.24 --,
- --CHR.sub.24 --CH.dbd.CH--CR.sub.23 R.sub.24 --CHR.sub.24 --,
- --CHR.sub.24 --CR.sub.23 R.sub.24 --CH.dbd.CH--CHR.sub.24 --,
- --CHR.sub.24 --C.dbd.C--CR.sub.23 R.sub.24 --CHR.sub.24 --, or
- --CHR.sub.24 --CR.sub.23 R.sub.24 --C.dbd.C --CHR.sub.24,
- the --CH.dbd.CH-- bond being cis or trans;
- R.sub.23 is hydrogen, (C.sub.1 -C.sub.18) linear alkyl, phenyl, hydroxy, (C.sub.1 -C.sub.18)alkoxy, aryloxy, aryl(C.sub.1 -.sub.18)alkyloxy, (C.sub.1 -C.sub.18)alkanoyloxy, hydroxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.18)alkoxy(C.sub.1 -C.sub.6)alkyl, phenyl(C.sub.1 -C.sub.6)alkyloxy, aryl(C.sub.1 -C.sub.18)alkyloxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.18)alkanoyloxy(C.sub.1 -C.sub.6)alkyl or ##STR134## where Z.sub.1 is lower alkyl, --OH, lower alkoxy, --CF.sub.3, --NO.sub.2, --NH.sub.2, or halogen, and p is as previously defined;
- R.sub.24 is hydrogen, (C.sub.1 -C.sub.18) linear alkyl, phenyl, hydroxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.18)alkoxy(C.sub.1 -C.sub.6)alkyl, phenyl (C.sub.1 -C.sub.6)alkyloxy, aryl(C.sub.1 -C.sub.18)alkyoxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.18)alkanoyloxy(C.sub.1 -C.sub.6)alkyl or ##STR135## where Z.sub.1 and p are as previously defined; R.sub.27 is hydrogen or R.sub.24 and R.sub.27 taken together with the carbon to which they are attached form C.dbd.O or C.dbd.S;
- R.sub.12 is selected from the group consisting of:
- hydrogen,
- alkyl,
- --C(.dbd.O)--(C.sub.1 -C.sub.18 straight chain or branched) alkyl,
- --C(.dbd.O)--NR.sub.13 R.sub.14,
- --C(.dbd.O)--NR.sub.15 R.sub.16,
- --S(.dbd.O).sub.2 --R.sub.17, and ##STR136## where R.sub.13 is selected from the group consisting of hydrogen and (C.sub.1 -C.sub.18)alkyl groups;
- where R.sub.14 is selected from the group consisting of hydrogen and (C.sub.1 -C.sub.18)alkyl groups;
- where NR.sub.15 R.sub.16 taken together form a ring structure selected from the group consisting of piperidinyl, morpholinyl and piperazinyl;
- where R.sub.4 is hydrogen, lower alkyl, lower alkoxy, hydroxy, tri(C.sub.1 -C.sub.6)alkylsilyloxy, hydroxy lower alkyl, alkanoyloxy lower alkyl, amino, mono- or dialkylamino, (C.sub.1 -C.sub.18)acyl amino, (C.sub.1 -C.sub.18)alkanoyl, trifluoromethyl, chlorine, fluorine, bromine, --O--C(.dbd.O)--(C.sub.1 -C.sub.18 straight or branched chain)alkyl or --C(.dbd.O)-aryl;
- where R.sub.17 is selected from the group consisting of (C.sub.1 -C.sub.18)alkyl and aryl groups;
- where aryl is phenyl or ##STR137## and where R.sub.6 is hydrogen, lower alkyl, lower alkoxy, hydroxy, chlorine, fluorine, bromine, iodine, lower monoalkylamino, lower dialkylamino, nitro, cyano, trifluoromethyl, or trifluoromethoxy;
- all geometric, optical, and stereoisomers thereof, or a pharmaceutically acceptable acid addition salt thereof.
- 2. An antipsychotic composition, which comprises the compound of claim 1 in an amount sufficient to produce an antipsychotic effect, and a pharmaceutically acceptable carrier therefor.
- 3. A method of treating psychoses, which comprises administering to a mammal a psychoses-treating effective amount of the compound of claim 1.
- 4. An analgesic composition, which comprises the compound of claim 1 in an amount sufficient to produce a pain-relieving effect, and a pharmaceutically acceptable carrier therefor.
- 5. A method of alleviating pain, which comprises administering to a mammal a pain-relieving effective amount of the compound of claim 1.
- 6. A depot pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 1, wherein the compound contains a hydroxy group, an amino group, or a nitrogen at the 1-position of an indazole ring, which has been acylated.
- 7. The depot pharmaceutical composition of claim 6, wherein the hydroxy group or amino group is acylated with an (C.sub.4 -C.sub.18)alkanoyl group or an (C.sub.4 -C.sub.18)alkoxycarbonyl group.
- 8. The composition of claim 6, which contains a pharmaceutically acceptable oil.
- 9. The composition of claim 8, wherein the oil is selected from the group consisting of coconut oil, peanut oil, sesame oil, cotton seed oil, corn oil, soybean oil, olive oil, and synthetic esters of fatty acids and polyfunctional alcohols.
- 10. The composition of claim 7, which contains a pharmaceutically acceptable oil.
- 11. The composition of claim 10, wherein the oil is selected from the group consisting of coconut oil, peanut oil, sesame oil, cotton seed oil, corn oil, soybean oil, olive oil, and synthetic esters of fatty acids and polyfunctional alcohols.
- 12. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 6 sufficient to produce a long acting antipsychotic effect.
- 13. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 7 sufficient to produce a long acting antipsychotic effect.
- 14. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 1 sufficient to produce a long acting antipsychotic effect.
CROSS-REFERENCE TO RELATED APPLICATION
This is a division of pending application Ser. No. 08/329,000 filed Oct. 25, 1994 of Joseph T. Strupczewski, Grover C. Helsley, Edward J. Glamkowski, Yulin Chiang, Kenneth J. Bordeau, Peter A. Nemoto and John J. Tegeler for HETEROARYLPIPERIDINES, PYRROLIDINES AND PIPERAZINES AND THEIR USE AS ANTIPSYCHOTICS AND ANALGETICS, which is a CIP application of Ser. No. 08/144,265, filed Oct. 28, 1993, abandoned which is a CIP application of Ser. No. 07/969,383, filed Oct. 30, 1992 U.S. Pat. No. 5,364,866, which is a CIP application of Ser. No. 07/788,269, filed Nov. 5, 1991, now abandoned, which is a CIP application of Ser. No. 07/944,705, filed Sep. 5, 1991, now abandoned, which is a continuation application of Ser. No. 07/619,825, filed Nov. 29, 1990, now abandoned, which is a continuation application of Ser. No. 07/456,790, filed Dec. 29, 1989, now abandoned, which is a CIP application of Ser. No. 07/354,411, filed May 19, 1989, now abandoned.
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4411901 |
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Divisions (1)
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Number |
Date |
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Parent |
329000 |
Oct 1994 |
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Continuations (2)
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Number |
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619825 |
Nov 1990 |
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Parent |
456790 |
Dec 1989 |
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Continuation in Parts (5)
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Number |
Date |
Country |
Parent |
144265 |
Oct 1993 |
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Parent |
969383 |
Oct 1992 |
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Parent |
788269 |
Nov 1991 |
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Parent |
944705 |
Sep 1991 |
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Parent |
354411 |
May 1989 |
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