.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: RE37478

« Back to Dashboard

Details for Patent: RE37478

Title: 1-(arylthioalkyl, arylaminoalkyl, or arylmethylenealkyl)-4-(heteroaryl)piperazines and related compounds useful as antipsychotics and analgesics
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): Strupczewski; Joseph T. (Fleming, NJ), Helsley; Grover C. (Stockton, NJ), Glamkowski; Edward J. (Warren, NJ), Chiang; Yulin (Convent Station, NJ), Bordeau; Kenneth J. (Kintersville, PA)
Assignee: Aventis Pharmaceuticals, Inc. (Kansas City, MO)
Filing Date:Dec 09, 1998
Application Number:09/207,910
Claims:1. A compound of the formula: ##STR133## ##STR134##

wherein

X is --O--, --S--, --NH--, or .[.--N(R.sub.2).]. .Iadd.--N(R.sub.2)--.Iaddend.;

R.sub.2 is selected from the group consisting of lower alkyl, aryl lower alkyl, aryl, cycloalkyl, aroyl, alkanoyl, .Iadd.alkoxycarbonyl, .Iaddend.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 --.]. .Iadd.--CR.sub.24 R.sub.27 --(CR.sub.23 R.sub.24).sub.n --CR.sub.24 R.sub.27 --, .Iaddend.where n is 0, 1, 2 or 3; or

.[.--CHR.sub.24 CH.dbd.CH--CHR.sub.24.]. .Iadd.--CHR.sub.24 --CH.dbd.CH--CHR.sub.24 --.Iaddend.,

--CHR.sub.24 --C.ident.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 --CH.ident.C--CR.sub.23 R.sub.24 --CHR.sub.24.]. .Iadd.--CHR.sub.24 --C.ident.C--CR.sub.23 R.sub.24 --CHR.sub.24 --.Iaddend., or

.[.--CHR.sub.24 --CR.sub.23 R.sub.24 --C.ident.C--CHR.sub.24.]. .Iadd.--CHR.sub.24 --CR.sub.23 R.sub.24 --C.ident.C--CHR.sub.24 --.Iaddend.,

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)alkoxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.18)alkanoyloxy(C.sub.1 -C.sub.18)alkyl or ##STR135##

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.]. .Iadd.alkyloxy.Iaddend.(C.sub.1 -C.sub.6)alkyl or (C.sub.1 -C.sub.18)alkanoyloxy(C.sub.1 -C.sub.6)alkyl or ##STR136##

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;

Q.sub.2 is .[.S, NH, or --CH.sub.2.]. .Iadd.--S--, --NH--, or --CH.sub.2 --.Iaddend.;

R is hydrogen, lower alkyl, lower alkoxy, hydroxyl, carboxyl, chlorine, fluorine, bromine, iodine, amino, lower mono or dialkylamino, nitro, lower alkyl thio, trifluoromethoxy, cyano, acylamino, trifluoromethyl, trifluoroacetyl, aminocarbonyl, monoalkylaminocarbonyl, .[.diakylaminocarbonyl.]. .Iadd.dialkylaminocarbonyl.Iaddend., formyl,

--C(.dbd.O)--alkyl,

--C(.dbd.O)--O-alkyl,

--C(.dbd.O)-aryl,

--C(.dbd.O)-heteroaryl,

--CH(OR.sub.7)-alkyl,

--C(.dbd.W)-alkyl,

--C(.dbd.W)-aryl, or

--C(.dbd.W)-heteroaryl;

alkyl is (C.sub.1 -C.sub.18)alkyl;

aryl is phenyl or ##STR137##

where

R.sub.5 is hydrogen, lower alkyl, lower alkoxy, hydroxy, chlorine, fluorine, bromine, iodine, lower .[.monoakylamino.]. .Iadd.monoalkylamino.Iaddend., lower dialkylamino, nitro, cyano, trifluoromethyl, or trifluoromethoxy;

heteroaryl is ##STR138##

Q.sub.3 is --O--, --S--, --NH--, --CH.dbd.N--;

W is CH.sub.2 or CHR.sub.8 or N--R.sub.9 ;

R.sub.7 is hydrogen, lower alkyl, or alkanoyl;

R.sub.8 is lower alkyl;

R.sub.9 is hydroxy, alkoxy, or --NHR.sub.10 ; and

R.sub.10 is hydrogen, lower alkyl, .[.C.sub.1 -C.sub.3 acyl.]. (.Iadd.C.sub.1 -C.sub.3)acyl.Iaddend., aryl, --C(.dbd.O)-aryl or --C(.dbd.O)--heteroaryl, where aryl and heteroaryl are as defined above; and

m is 1, 2 or 3;

.[.with the exclusion of a compound wherein X is --S--, Q.sub.2 is --CH.sub.2 --, Y is hydrogen, lower alkyl, lower alkoxy, halogen, hydroxy or trifluoromethyl, and p is 1 or 2;

with the exclusion of a compound wherein X is --N(R.sub.2)--, Q.sub.2 is --CH.sub.2 --, R is chlorine, fluorine, bromine, iodine, lower alkyl, lower alkoxy, lower alkyl thio, lower monoalkylamino, lower dialkylamino, amino, cyano, hydroxy, or trifluoromethyl, R.sub.2 is aryl, Y is hydrogen, halogen, lower alkyl, lower alkoxy or hydroxy, and p is 1 or 2;

with the exclusion of a compound wherein X is --NH-- or --N(R.sub.2)--, R.sub.2 is lower alkyl, aryl lower alkyl, or phenylsulfonyl, Y is hydrogen, halogen, lower alkyl, lower alkoxy, or hydroxy, p is 1 or 2; and Q.sub.2 is --CH.sub.2 --;.].

.Iadd.with the proviso that R.sub.23 is not hydrogen, (C.sub.1 -C.sub.18)linear alkyl, phenyl, or ##STR139##

when R.sub.27 is hydrogen and R.sub.24 is hydrogen, (C.sub.1-C.sub.18)linear alkyl, phenyl, or ##STR140##

with the proviso that R.sub.24 is not hydrogen, (C.sub.1 -C.sub.18)linear alkyl, phenyl, or ##STR141##

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 ##STR142##

or when R.sub.1 is --CHR.sub.24 --CH.dbd.CH--CHR.sub.24 -- or --CHR.sub.24 --C.ident.C--CHR.sub.24 --;

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 by acylated with a (C.sub.4 -C.sub.18)alkoxycarbonyl group; and.Iaddend.

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 compound of claim 1, wherein R.sub.2 is (C.sub.1 -C.sub.18)alkanoyl or (C.sub.1 -C.sub.18)alkoxycarbonyl.

4. 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.

5. A method of treating psychoses, which comprises administrating to a mammal a psychoses-treating effective amount of the compound of claim 1.

6. 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.

7. A method of alleviating pain, which comprises administering to a mammal a pain-relieving effective amount of the compound of claim 1.

8. 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.

9. The depot pharmaceutical composition of claim 8, 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.

10. The composition of claim 8, 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 ester of fatty acids and polyfunctional alcohols.

12. The composition of claim 9, which contains a pharmaceutically acceptable oil.

13. The composition of claim 12, 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 esters of fatty acids and polyfunctional alcohols.

14. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 8 sufficient to produce a long acting antipsychotic effect.

15. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 9 sufficient to produce a long acting antipsychotic effect.

16. 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..Iadd.

17. A compound of the formula ##STR143##

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, when p is 1;

Y is lower alkoxy, 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.ident.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.ident.C--CH.sub.2 --CH.sub.2 --, or

--CH.sub.2 --CH.sub.2 --C.ident.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 ##STR144##

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; and

Q.sub.2 is --S--, --NH--, or --CH.sub.2 --;

R is hydrogen, lower alkyl, lower alkoxy, hydroxyl, carboxyl, chlorine, fluorine, bromine, iodine, amino, lower mono or dialkylamino, nitro, lower alkyl thio, trifluoromethoxy, cyano, acylamino, trifluoromethyl, trifluoroacetyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, formyl,

--C(.dbd.O)-alkyl

--C(.dbd.O)--O-alkyl,

--C(.dbd.O)-aryl,

--C(.dbd.O)-heteroaryl,

--CH(OR.sub.7)-alkyl,

--C(.dbd.W)-alkyl,

--C(.dbd.W)-aryl, or

--C(.dbd.W)-heteroaryl;

alkyl is (C.sub.1 -C.sub.6)alkyl;

aryl is phenyl or ##STR145##

where

R.sub.5 is hydrogen, lower alkyl, lower alkoxy, hydroxy, chlorine, fluorine, bromine, iodine, lower monoalkylamino, lower dialkylamino, nitro, cyano, trifluoromethyl, or trifluoromethoxy;

heteroaryl is ##STR146##

Q.sub.3 is --O--, --S--, --NH--, or --CH.dbd.N--;

W is CH.sub.2, CHR.sub.8 or N--R.sub.9 ;

R.sub.7 is hydrogen, lower alkyl, or acyl;

R.sub.8 is lower alkyl;

R.sub.9 is hydroxy, alkoxy, or --NHR.sub.10 ; and

R.sub.10 is hydrogen, lower alkyl, (C.sub.1 -C.sub.3)acyl, aryl, --C(.dbd.O)-aryl, or --C(.dbd.O)-heteroaryl, where aryl and heteroaryl are as defined above; and

m is 1, 2 or 3;

with the proviso that Q.sub.2 is not --CH.sub.2 -- when X is --S-- and Y is hydrogen, lower alkyl, lower alkoxy, halogen, hydroxy or trifluoromethyl;

with the proviso that Q.sub.2 is not --CH.sub.2 -- when X is --N(R.sub.2)--, R.sub.2 is aryl, and R is hydrogen, chlorine, fluorine, bromine, iodine, lower alkyl, lower alkoxy, lower alkyl thio, lower monoalkylamino, lower dialkylamino, amino, nitro, cyano, hydroxy, or trifluoromethyl;

with the proviso that Q.sub.2 is not --CH.sub.2 -- when X is --NH-- or --N(R.sub.2)--, where R.sub.2 is lower alkyl, aryl lower alkyl, or phenylsulfonyl;

all geometric, optical, and stereoisomers thereof, or a pharmaceutically acceptable acid addition salt thereof..Iaddend..Iadd.

18. A pharmaceutical composition which comprises a compound of claim 17 and a pharmaceutically acceptable carrier therefor..Iaddend..Iadd.

19. The compound of claim 17, wherein X is --N(R.sub.2)--..Iaddend..Iadd.

20. The compound of claim 17, wherein R.sub.2 is (C.sub.2 -C.sub.11)alkanoyl..Iaddend..Iadd.

21. An antipsychotic composition, which comprises the compound of claim 17 in an amount sufficient to produce an antipsychotic effect, and a pharmaceutically acceptable carrier therefor..Iaddend..Iadd.

22. A method of treating psychoses, which comprises administrating to a mammal a psychoses-treating effective amount of the compound of claim 17..Iaddend..Iadd.

23. An analgesic composition, which comprises the compound of claim 17 in an amount sufficient to produce a pain-relieving effect, and a pharmaceutically acceptable carrier therefor..Iaddend..Iadd.

24. A method of alleviating pain, which comprises administering to a mammal a pain-relieving effective amount of the compound of claim 17..Iaddend..Iadd.

25. A depot pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of 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, 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, when p is 1;

Y is lower alkoxy, 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.ident.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.ident.C--CH.sub.2 --CH.sub.2 --, or

--CH.sub.2 --CH.sub.2 --C.ident.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 ##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; and

Q.sub.2 is --S--, --NH--, or --CH.sub.2 --;

R is hydrogen, lower alkyl, lower alkoxy, hydroxyl, carboxyl, chlorine, fluorine, bromine, iodine, amino, lower mono or dialkylamino, nitro, lower alkyl thio, trifluoromethoxy, cyano, acylamino, trifluoromethyl, trifluoroacetyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, formyl,

--C(.dbd.O)-alkyl

--C(.dbd.O)--O-alkyl,

--C(.dbd.O)-aryl,

--C(.dbd.O)-heteroaryl,

--CH(OR.sub.7)-alkyl,

--C(.dbd.W)-alkyl,

--C(.dbd.W)-aryl, or

--C(.dbd.W)-heteroaryl;

alkyl is (C.sub.1 -C.sub.6)alkyl;

aryl is phenyl or ##STR149##

where

R.sub.5 is hydrogen, lower alkyl, lower alkoxy, hydroxy, chlorine, fluorine, bromine, iodine, lower monoalkylamino, lower dialkylamino, nitro, cyano, trifluoromethyl, or trifluoromethoxy;

heteroaryl is ##STR150##

Q.sub.3 is --O--, --S--, --NH--, or --CH.dbd.N--;

W is CH.sub.2, CHR.sub.8, or N--R.sub.9 ;

R.sub.7 is hydrogen, lower alkyl, or acyl;

R.sub.8 is lower alkyl;

R.sub.9 is hydroxy, alkoxy, or --NHR.sub.10 ; and

R.sub.10 is hydrogen, lower alkyl, (C.sub.1 -C.sub.3)acyl, aryl, --C(.dbd.O)-aryl or --C(.dbd.O)-heteroaryl, where aryl and heteroaryl are as defined above; and

m is 1, 2 or 3;

with the proviso that Q.sub.2 is not --CH.sub.2 -- when X is --S-- and Y is hydrogen, lower alkyl, lower alkoxy, halogen, hydroxy or trifluoromethyl;

with the proviso that Q.sub.2 is not --CH.sub.2 -- when X is --N(R.sub.2)--, R.sub.2 is aryl, and R is hydrogen, chlorine, fluorine, bromine, iodine, lower alkyl, lower alkoxy, lower alkyl thio, lower monoalkylamino, lower dialkylamino, amino, nitro, cyano, hydroxy, or trifluoromethyl;

with the proviso that Q.sub.2 is not --CH.sub.2 -- when X is --NH-- or --N(R.sub.2)--, where R.sub.2 is lower alkyl, aryl lower alkyl, or phenylsulfonyl;

wherein 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; and

all geometric, optical, and stereoisomers thereof, or a pharmaceutically acceptable acid addition salt thereof..Iaddend..Iadd.

26. The depot pharmaceutical composition of claim 25, 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..Iaddend..Iadd.

27. The depot composition of claim 25, which contains a pharmaceutically acceptable oil..Iaddend..Iadd.

28. The depot composition of claim 27, 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 ester of fatty acids and polyfunctional alcohols..Iaddend..Iadd.

29. The depot composition of claim 26, which contains a pharmaceutically acceptable oil..Iaddend..Iadd.

30. The depot composition of claim 29, 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 esters of fatty acids and polyfunctional alcohols..Iaddend..Iadd.

31. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 25 sufficient to produce a long acting antipsychotic effect..Iaddend..Iadd.

32. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 26 sufficient to produce a long acting antipsychotic effect..Iaddend..Iadd.

33. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 30 sufficient to produce a long acting antipsychotic effect..Iaddend..Iadd.

34. A compound of the formula: ##STR151##

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, alkoxycarbonyl, and phenylsulfonyl groups;

aryl is as defined hereinafter;

p is 2;

Y is lower alkyl, hydroxy, chlorine, fluorine, bromine, iodine, lower alkoxy, trifluoromethoxy, nitro or amino when X is --S--, --NH--, or --N(R.sub.2)--;

Y is lower alkyl, trifluoromethoxy, 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.ident.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.ident.C--CR.sub.23 R.sub.24 --CHR.sub.24 --, or

--CHR.sub.24 --CR.sub.23 R.sub.24 --C.ident.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, aryl(C.sub.1 -C.sub.18)alkoxy(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.18)alkanoyloxy(C.sub.1 -C.sub.18)alkyl or ##STR152##

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)alkyloxy(C.sub.1 -C.sub.6)alkyl or (C.sub.1 -C.sub.18)alkanoyloxy(C.sub.1 -C.sub.6)alkyl or ##STR153##

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;

O.sub.2 is --S--, --NH--, or --CH.sub.2 --;

R is hydrogen, lower alkyl, lower alkoxy, hydroxyl, carboxyl, chlorine, fluorine, bromine, iodine, amino, lower mono or dialkylamino, nitro, lower alkyl thio, trifluoromethoxy, cyano, acylamino, trifluoromethyl, trifluoroacetyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, formyl,

--C(.dbd.O)-alkyl

--C(.dbd.O)--O-alkyl,

--C(.dbd.O)-aryl,

--C(.dbd.O)-heteroaryl,

--CH(OR.sub.7)-alkyl,

--C(.dbd.W)-alkyl,

--C(.dbd.W)-aryl, or

--C(.dbd.W)-heteroaryl;

alkyl is (C.sub.1 -C.sub.18)alkyl;

aryl is phenyl or ##STR154##

where

R.sub.5 is hydrogen, lower alkyl, lower alkoxy, hydroxy, chlorine, fluorine, bromine, iodine, lower monoalkylamino, lower dialkylamino, nitro, cyano, trifluoromethyl, or trifluoromethoxy;

heteroary is ##STR155##

Q.sub.3 is --O--, --S--, --NH--, --CH.dbd.N--;

W is CH.sub.2 or CHR.sub.8 or N--R.sub.9 ;

R.sub.7 is hydrogen, lower alkyl, or alkanoyl;

R.sub.8 is lower alkyl;

R.sub.9 is hydroxy, alkoxy, or --NHR.sub.10 ; and

R.sub.10 is hydrogen, lower alkyl, (C.sub.1 -C.sub.3)acyl, aryl, --C(.dbd.O)-aryl or --C(.dbd.O)-heteroaryl, where aryl and heteroaryl are as defined above; and

m is 1, 2 or 3;

with the proviso that Q.sub.2 is not --CH.sub.2 -- when X is --S-- and Y is hydrogen, lower alkyl, lower alkoxy, halogen, hydroxy or trifluoromethyl;

with the proviso that Q.sub.2 is not --CH.sub.2 -- when X is --NH-- or --N(R.sub.2)--, where R.sub.2 is lower alkyl, aryl lower alkyl, or phenylsulfonyl;

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 alternately be acylated with a (C.sub.4 -C.sub.18)alkoxycarbonyl group; and

all geometric, optical, and stereoisomers thereof, or a pharmaceutically acceptable acid addition salt thereof..Iaddend..Iadd.

35. The compound of claim 34, wherein X is --N(R.sub.2)--..Iaddend..Iadd.

36. The compound of claim 34, wherein R.sub.2 is (C.sub.1 -C.sub.18)alkanoyl or (C.sub.1 -C.sub.18)alkoxycarbonyl..Iaddend..Iadd.

37. An antipsychotic composition, which comprises the compound of claim 34 in an amount sufficient to produce an antipsychotic effect, and a pharmaceutically acceptable carrier therefor..Iaddend..Iadd.

38. A method of treating psychoses, which comprises administrating to a mammal a psychoses-treating effective amount of the compound of claim 34..Iaddend..Iadd.

39. An analgesic composition, which comprises the compound of claim 34 in an amount sufficient to produce a pain-relieving effect, and a pharmaceutically acceptable carrier therefor..Iaddend..Iadd.

40. A method of alleviating pain, which comprises administering to a mammal a pain-relieving effective amount of the compound of claim 34..Iaddend..Iadd.

41. A depot pharmaceutical composition, which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 34, wherein 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..Iaddend..Iadd.

42. The depot pharmaceutical composition of claim 41, 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)alkyloxycarbonyl group..Iaddend..Iadd.

43. The composition of claim 41, which contains a pharmaceutically acceptable oil..Iaddend..Iadd.

44. The composition of claim 43, 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 ester of fatty acids and polyfunctional alcohols..Iaddend..Iadd.

45. The composition of claim 42, which contains a pharmaceutically acceptable oil..Iaddend..Iadd.

46. The composition of claim 45, 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 esters of fatty acids and polyfunctional alcohols..Iaddend..Iadd.

47. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 41 sufficient to produce a long acting antipsychotic effect..Iaddend..Iadd.

48. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 42 sufficient to produce a long acting antipsychotic effect..Iaddend..Iadd.

49. A method for providing a long acting antipsychotic effect, which comprises injecting into a mammal an amount of the composition of claim 46 sufficient to produce a long acting antipsychotic effect..Iaddend.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc