Details for Patent: 5,874,435

Title:	4-heteroaryl-1-piperazinealkanols and derivatives thereof and their therapeutic utility
Abstract:	Heteroarylpiperidines, pyrrolidines, and piperazines are useful as antipsychotic and analgesic agents. the compounds are especially useful for treating psychoses by administering to a mammal a psychoses-treating effective amount of one of the compounds. Depot derivatives of the compounds are useful for providing long acting effects of the compounds. The compounds are also useful as analgesics by administering a pain-relieving effective amount of one of the compounds to a mammal.
Inventor(s):	Glamkowski; Edward J. (Warren, NJ), Chiang; Yulin (Covent Station, NJ), Strupczewski; Joseph T. (Flemington, NJ), Bordeau; Kenneth J. (Kintnersville, PA), Nemoto; Peter A. (Raritan, NJ), Tegeler; John J. (Bridgewater, NJ)
Assignee:	Hoechst Marion Roussel, Inc. (Kansas City, MO)
Filing Date:	Jun 06, 1995
Application Number:	08/470,039
Claims:	1. A compound having the formula: ##STR133## wherein, X is --O--, --S--, ##STR134## R.sub.2 is selected from the group consisting of lower alkyl, aryl lower alkyl, aryl, cycloalkyl, aroyl, alkanoyl, and phenylsulfonyl groups, wherein 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, when p is 1; Y is lower alkyl, hydroxy or halogen when p is 2 and X is --O--; in which (R.sub.1) is R.sub.20, R.sub.21 or R.sub.22, wherein: R.sub.20 is --(CH.sub.2).sub.n --, where n is 2, 3, 4 or 5; R.sub.21 is --CH.sub.2 --CH.dbd.CH--CH.sub.2 --, --CH.sub.2 --C.tbd.C--CH.sub.2 --, --CH.sub.2 --CH.dbd.CH--CH.sub.2 --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --CH.dbd.CH--CH.sub.2 --, --CH.sub.2 --C.tbd.C--CH.sub.2 --CH.sub.2 --, or --CH.sub.2 --CH.sub.2 --C.tbd.C--CH.sub.2 --, the --CH.dbd.CH-- bond being cis or trans; R.sub.22 is R.sub.20 or R.sub.21 in which one or more carbon atoms of R.sub.20 or R.sub.21 are substituted by at least one C.sub.1 -C.sub.6 linear alkyl group, phenyl group or ##STR135## where Z.sub.1 is lower alkyl, --OH, lower alkoxy, --CF.sub.3, --NO.sub.2, --NH.sub.2 or halogen; where R.sub.12 is selected from the group consisting of: hydrogen, ##STR136## where R.sub.13 is selected from the group consisting of hydrogen and (C.sub.1 -C.sub.12) alkyl groups; where R.sub.14 is selected from the group consisting of hydrogen and (C.sub.1 -C.sub.12) 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.17 is selected from the group consisting of lower alkyl and aryl groups; in which aryl is phenyl or ##STR137## where R.sub.5 is hydrogen, lower alkyl, lower alkoxy, hydroxy, chlorine, fluorine, bromine, iodine, lower monoalkylamino, lower dialkylamino, nitro, cyano, trifluoromethyl, or trifluoromethoxy; with the proviso that R.sub.12 is not H when X is --NH-- or --NR.sub.2 --, where R.sub.2 is loweralkyl, or aryl aryl loweralkyl, aroyl, alkanoyl, or phenylsulfonyl, Y is hydrogen, loweralkyl, loweralkoxy, chlorine, fluorine, bromine, iodine, or a hydroxyl group, and p is 1 or 2; all geometric, optical, and stereoisomers thereof, or a pharmaceutically acceptable acid addition salt thereof. 2. The compound of claim 1, wherein X is --N(R.sub.2)--. 3. The compoud of claim 2, wherein R.sub.2 is C.sub.2 -C.sub.11)alkanoyl. 4. The compound of claim 1, wherein R.sub.12 is hydrogen. 5. The compound of claim 4, wherein X is --O--. 6. The compound of claim 4, wherein X is --S--. 7. The compound of claim 1, wherein R.sub.12 is --C(.dbd.O)--(C.sub.1 -C.sub.12)alkyl. 8. The compound of claim 7, wherein X is --O--. 9. An antipsychotic composition, which comprises the compound of claim 1 in an amount sufficient to produce an antipsychotic effect and a pharmaceutically acceptable carrier. 10. A method of treating psychoses, which comprises administering to a mammal a psychoses-treating amount of the compound of claim 1. 11. 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. 12. A method of alleviating pain, which comprises administering to a mammal a pain-relieving effective amount of the compound of claim 1. 13. 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 an acylated hydroxy group, or an acylated amino group. 14. The depot pharmaceutical composition of claim 13 wherein the hydroxy group is acylated with a (C.sub.4 -C.sub.18)alkanoyl group or the amino group is acylated with an (C.sub.4 -C.sub.18)alkanoyl group or an (C.sub.4 -C.sub.18)alkoxycarbonyl group. 15. The composition of claim 13, which contains a pharmaceutically acceptable oil. 16. The composition of claim 15, 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. 17. The composition of claim 14, which contains a pharmaceutically acceptable oil. 18. The composition of claim 17, 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. 19. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 13 sufficient to produce a long acting antipsychotic effect. 20. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 14 sufficient to produce a long acting antipsychotic effect. 21. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 18 sufficient to produce a long acting antipsychotic effect. 22. A pharmaceutical composition which comprises the compound of claim 1 and a pharmaceutically acceptable carrier therefor. 23. A compound of the formula: ##STR138## 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, (C.sub.3 -C.sub.10)cycloalkyl, aroyl, (C.sub.2 -C.sub.18)alkanoyl, (C.sub.1 -C.sub.18)alkoxycarbonyl, 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, trifluoroethyl, nitro, or amino; R.sub.1 is --CR.sub.24 R.sub.27 --(CR.sub.23 R.sub.24).sub.n --CR.sub.24 R.sub.27 --, where n is 0, 1, 2, or 3; or --CHR.sub.24 CH.dbd.CH--CHR.sub.24 --, --CHR.sub.24 --C.tbd.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.tbd.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 -C.sub.18)alkyloxy, (C.sub.2 -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.2 -C.sub.18)alkanoyloxy(C.sub.1 -C.sub.6)alkyl ##STR139## 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, wherein aryl is as defined hereinafter; 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)alkoxy (C.sub.1 -C.sub.6)alkyl, (C.sub.2 -C.sub.18)alkanoyloxy(C.sub.1 -C.sub.6)alkyl ##STR140## where Z.sub.1 and p are as previously defined, wherein aryl is as defined hereinafter; R.sub.21 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; with the proviso that R.sub.23 is not hydrogen, (C.sub.1 -C.sub.18) linear alkyl, phenyl, or ##STR141## when R.sub.27 is hydrogen and R.sub.24 is hydrogen, (C.sub.1 -C.sub.18) linear alkyl, phenyl, or ##STR142## with the proviso that R.sub.24 is not hydrogen, (C.sub.1 -C.sub.18) linear alkyl, phenyl, or ##STR143## when R.sub.27 is hydrogen and n is 0, or when R.sub.27 is hydrogen and R.sub.23 is hydrogen, (C.sub.1 -C.sub.18) linear alkyl, phenyl, or ##STR144## or when R.sub.1 is --CHR.sub.24 --CH.dbd.CH--CHR.sub.24 -- or --CHR.sub.24 --C.tbd.C--CHR.sub.24 ; 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 ##STR145## 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.17 is selected from the group consisting of (C.sub.1 -C.sub.18)alkyl and aryl groups; 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, nitro, mono- or dialkylamino, (C.sub.1 -C.sub.18)acylamino, (C.sub.2 -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 m is 1, 2, or 3; aryl is phenyl or ##STR146## wherein R.sub.5 is hydrogen, lower alkyl, lower alkoxy, hydroxy, chlorine, fluorine, bromine, iodine, lower monoalkylamino, lower dialkylamino, nitro, cyano, trifluoromethyl, or trifluoromethoxy; and, any hydroxyl group attached to an aliphatic or aromatic carbon atom, or any primary or secondary nitrogen atom may be acylated with a (C.sub.4 -C.sub.18)alkanoyl group, in addition, any nitrogen atom may alternatively be acylated with a (C.sub.4 -C.sub.18)alkoxycarbonyl group; with the proviso that R.sub.12 is not H when X is --NH-- or --NR.sub.2 --, where R.sub.2 is loweralkyl, aryl loweralkyl, aroyl, alkanoyl, or phenylsulfonyl, Y is hydrogen, loweralkyl, loweralkoxy, chlorine, fluorine, bromine, iodine, or a hydroxyl group, and p is 1 or 2; all geometric, optical, and stereoisomers thereof, or a pharmaceutically acceptable acid addition salt thereof. 24. The compound of claim 23, wherein X is --N(R.sub.2)--. 25. The compound of claim 24, wherein R.sub.2 is (C.sub.2 -C.sub.18)alkanoyl or (C.sub.1 -C.sub.18)alkoxycarbonyl. 26. The compound of claim 23, wherein R.sub.12 is hydrogen. 27. The compound of claim 26, wherein X is --O--. 28. The compound of claim 26, wherein X is --S--. 29. The compound of claim 23, wherein R.sub.12 is --C(.dbd.O)--(C.sub.1 -C.sub.18)alkyl. 30. The compound of claim 29, wherein X is --O--. 31. An antipsychotic composition, which comprises the compound of claim 23 in an amount sufficient to produce an antipsychotic effect and a pharmaceutically acceptable carrier. 32. A method of treating psychoses, which comprises administering to a mammal a psychoses-treating amount of the compound of claim 23. 33. An analgesic composition, which comprises the compound of claim 23 in an amount sufficient to produce a pain-relieving effect and a pharmaceutically acceptable carrier. 34. A method of alleviating pain, which comprises administering to a mammal a pain-relieving effective amount of the compound of claim 23. 35. A depot pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 23, wherein the compound contains an acylated hydroxy group, or an acylated amino group. 36. The depot pharmaceutical composition of claim 35, wherein the hydroxy group is acylated with a (C.sub.4 -C.sub.18)alkanoyl group, or the amino group is acylated with a (C.sub.4 -C.sub.18)alkanoyl group or a (C.sub.4 -C.sub.18)alkoxycarbonyl group. 37. The composition of claim 35, which contains a pharmaceutically acceptable oil. 38. The composition of claim 37, wherein the oil is selected from the group consisting of coconut oil, peanut oil, sesame oil, cottonseed oil, corn oil, soybean oil, olive oil, and esters of fatty acids and polyfunctional alcohols. 39. The composition of claim 36, which contains a pharmaceutically acceptable oil. 40. The composition of claim 39, wherein the oil is selected from the group consisting of coconut oil, peanut oil, sesame oil, cottonseed oil, corn oil, soybean oil, olive oil, and esters of fatty acids and polyfunctional alcohols. 41. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 35 sufficient to produce a long acting antipsychotic effect. 42. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 36 sufficient to produce a long acting antipsychotic effect. 43. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 40 sufficient to produce a long acting antipsychotic effect. 44. A compound of the formula: ##STR147## 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, (C.sub.3 -C.sub.10)cycloalkyl, aroyl, (C.sub.2 -C.sub.18)alkanoyl, (C.sub.1 -C.sub.18)alkoxycarbonyl, and phenylsulfonyl groups; aryl is as defined hereinafter; p is 2; Y is lower alkyl, hydroxy, chlorine, fluorine, bromine, iodine, lower alkoxy, trifluoromethyl, nitro, or amino when X is --S--, --NH--, or --N(R.sub.2)--; Y is lower alkyl, trifluoromethyl, nitro, or amino when X is --O--; R.sub.1 is --CR.sub.24 R.sub.27 --(CR.sub.23 R.sub.24).sub.n --CR.sub.24 R.sub.27 --, where n is 0, 1, 2 or 3; or --CHR.sub.24 CH.dbd.CH--CHR.sub.24 --, --CHR.sub.24 --C.tbd.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.tbd.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 -C.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.2 -C.sub.18)alkanoyloxy (C.sub.1 -C.sub.6)alkyl ##STR148## 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, wherein aryl is as defined hereinafter; 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)alkoxy (C.sub.1 -C.sub.6)alkyl, (C.sub.2 -C.sub.18)alkanoyloxy (C.sub.1 -C.sub.6)alkyl ##STR149## where Z.sub.1 and p are as previously defined, wherein aryl is as defined hereinafter; 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 ##STR150## 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.17 is selected from the group consisting of (C.sub.1 -C.sub.18)alkyl and aryl groups; 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, nitro, mono- or dialkylamino, C.sub.2 -C.sub.18)acylamino, (C.sub.2 -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 m is 1, 2, or 3; aryl is phenyl or ##STR151## wherein R.sub.5 is hydrogen, lower alkyl, lower alkoxy, hydroxy, chlorine, fluorine, bromine, iodine, lower monoalkylamino, lower dialkylamino, nitro, cyano, trifluoromethyl, or trifluoromethoxy; and, any hydroxyl group attached to an aliphatic or aromatic carbon atom, or any primary or secondary nitrogen atom may be acylated with a (C.sub.4 -C.sub.18)alkanoyl group, in addition, any nitrogen atom may alternatively be acylated with a (C.sub.4 -C.sub.18)alkoxycarbonyl group; with the proviso that R.sub.12 is not H when X is --NH-- or --NR.sub.2 --, where R.sub.2 is loweralkyl, aryl, loweralkyl, aroyl, alkanoyl, or phenylsulfonyl, and Y is loweralkyl, loweralkoxy, chlorine, fluorine, bromine, iodine, or a hydroxyl group; with the proviso that R.sub.12 is not ##STR152## when X is O or S; Y is lower alkyl, lower alkoxy, chlorine, fluorine, bromine, iodine, or a hydroxyl group; and R.sub.1 is --CR.sub.24 R.sub.27 --(CR.sub.23 R.sub.24).sub.n --CR.sub.24 R.sub.27, where R.sub.23 and R.sub.24 are each hydrogen or (C.sub.1 -C.sub.18) linear alkyl and R.sub.27 is hydrogen; all geometric, optical, and stereoisomers thereof, or a pharmaceutically acceptable acid addition salt thereof. 45. The compound of claim 44, wherein X is --N(R.sub.2)--. 46. The compound of claim 45, wherein R.sub.2 is (C.sub.2 -C.sub.18)alkanoyl or (C.sub.1 -C.sub.18)alkoxycarbonyl. 47. The compound of claim 44, wherein R.sub.12 is hydrogen. 48. The compound of claim 47, wherein X is --O--. 49. The compound of claim 49, wherein X is --S--. 50. The compound of claim 44, wherein R.sub.12 is --C(.dbd.O)--(C.sub.1 -C.sub.18)alkyl. 51. The compound of claim 50, wherein X is --O--. 52. An antipsychotic composition, which comprises the compound of claim 44 in an amount sufficient to produce an antipsychotic effect and a pharmaceutically acceptable carrier. 53. A method of treating psychoses, which comprises administering to a mammal a psychoses-treating amount of the compound of claim 44. 54. An analgesic composition, which comprises the compound of claim 44 in an amount sufficient to produce a pain-relieving effect and a pharmaceutically acceptable carrier. 55. A method of alleviating pain, which comprises administering to a mammal a pain-relieving effective amount of the compound of claim 44. 56. A depot pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 44, wherein the compound contains an acylated hydroxy group, or an acylated amino group. 57. The depot pharmaceutical composition of claim 56, wherein the hydroxy group is acylated with a (C.sub.4 -C.sub.18)alkanoyl group, or the amino group is acylated with a (C.sub.4 -C.sub.18)alkanoyl group or a (C.sub.4 -C.sub.18)alkoxycarbonyl group. 58. The composition of claim 56, which contains a pharmaceutically acceptable oil. 59. The composition of claim 58, wherein the oil is selected from the group consisting of coconut oil, peanut oil, sesame oil, cottonseed oil, corn oil, soybean oil, olive oil, and esters of fatty acids and polyfunctional alcohols. 60. The composition of claim 57, which contains a pharmaceutically acceptable oil. 61. The composition of claim 60, wherein the oil is selected from the group consisting of coconut oil, peanut oil, sesame oil, cottonseed oil, corn oil, soybean oil, olive oil, and esters of fatty acids and polyfunctional alcohols. 62. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 56 sufficient to produce a long acting antipsychotic effect. 63. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 57 sufficient to produce a long acting antipsychotic effect. 64. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 61 sufficient to produce a long acting antipsychotic effect. 65. A compound of the formula: ##STR153## 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, (C.sub.3 -C.sub.10)cycloalkyl, aroyl, (C.sub.2 -C.sub.18)alkanoyl, (C.sub.1 -C.sub.18)alkoxycarbonyl, 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.24).sub.n --CR.sub.24 R.sub.27 --, where n is 0, 1, 2 or 3; or --CHR.sub.24 CH.dbd.CH--CHR.sub.24 --, --CHR.sub.24 --C.tbd.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.tbd.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 -C.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.2 -C.sub.18)alkanoyloxy (C.sub.1 -C.sub.6)alkyl ##STR154## 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, wherein aryl is as defined hereinafter; 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)alkoxy(C.sub.1 -C.sub.6)alkyl, (C.sub.2 -C.sub.18)alkanoyloxy (C.sub.1 -C.sub.6) alkyl ##STR155## where Z.sub.1 and p are as previously defined, wherein aryl is as defined hereinafter; 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; with the proviso that when R.sub.1 is --CR.sub.24 R.sub.27 --(CR.sub.23 R.sub.24).sub.n --CR.sub.24 R.sub.27 --and n is not 0, R.sub.23 is not hydrogen or (C.sub.1 -C.sub.18) linear alkyl when R.sub.24 is hydrogen or (C.sub.1 -C.sub.18) linear alkyl and R.sub.27 is hydrogen; with the proviso that when R.sub.1 is --CR.sub.24 R.sub.27 --(CR.sub.23 R.sub.24).sub.n --CR.sub.24 R.sub.27 --and n is 0, R.sub.24 is not hydrogen or (C.sub.1 -C18) linear alkyl when R.sub.27 is hydrogen; R.sub.12 is ##STR156## 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, nitro, mono- or dialkylamino, (C.sub.2 -C.sub.18)acylamino, (C.sub.2 -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 m is 1, 2, or 3; aryl is phenyl or ##STR157## wherein R.sub.5 is hydrogen, lower alkyl, lower alkoxy, hydroxy, chlorine, fluorine, bromine, iodine, lower monoalkylamino, lower dialkylamino, nitro, cyano, trifluoromethyl, or trifluoromethoxy; and, any hydroxyl group attached to an aliphatic or aromatic carbon atom, or any primary or secondary nitrogen atom may be acylated with a (C.sub.4 -C.sub.18)alkanoyl group, in addition, any nitrogen atom may alternatively be acylated with a (C.sub.4 -C.sub.18)alkoxycarbonyl group; all geometric, optical, and stereoisomers thereof, or a pharmaceutically acceptable acid addition salt thereof. 66. The compound of claim 65, wherein X is --N(R.sub.2)--. 67. The compound of claim 66, wherein R.sub.2 is (C.sub.2 -C.sub.18)alkanoyl or (C.sub.1 -C.sub.18)alkoxycarbonyl. 68. The compound of claim 65, wherein X is --O--. 69. An antipsychotic composition, which comprises the compound of claim 65 in an amount sufficient to produce an antipsychotic effect and a pharmaceutically acceptable carrier. 70. A method of treating psychoses, which comprises administering to a mammal a psychoses-treating amount of the compound of claim 65. 71. An analgesic composition, which comprises the compound of claim 65 in an amount sufficient to produce a pain-relieving effect and a pharmaceutically acceptable carrier. 72. A method of alleviating pain, which comprises administering to a mammal a pain-relieving effective amount of the compound of claim 65. 73. A depot pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 65, wherein the compound contains an acylated hydroxy group, or an acylated amino group. 74. The depot pharmaceutical composition of claim 73, wherein the hydroxy group is acylated with a (C.sub.4 -C.sub.18)alkanoyl group, or the amino group is acylated with a (C.sub.4 -C.sub.18)alkanoyl group or a (C.sub.4 -C.sub.18)alkoxycarbonyl group. 75. The composition of claim 74, which contains a pharmaceutically acceptable oil. 76. The composition of claim 75, wherein the oil is selected from the group consisting of coconut oil, peanut oil, sesame oil, cottonseed oil, corn oil, soybean oil, olive oil, and esters of fatty acids and polyfunctional alcohols. 77. The composition of claim 74, which contains a pharmaceutically acceptable oil. 78. The composition of claim 77, wherein the oil is selected from the group consisting of coconut oil, peanut oil, sesame oil, cottonseed oil, corn oil, soybean oil, olive oil, and esters of fatty acids and polyfunctional alcohols. 79. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 73 sufficient to produce a long acting antipsychotic effect. 80. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 74 sufficient to produce a long acting antipsychotic effect. 81. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 75 sufficient to produce a long acting antipsychotic effect.