Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1992-02-20
1994-09-27
Bond, Robert T.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544121, 544363, 544364, 514255, 5142352, 540523, A61K 3155, C07D41714
Patent
active
053507479
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention is directed to novel heteroaryl piperazine compounds of the formula I, depicted below, which exhibit neuroleptic activity and are useful in the treatment of psychosis and anxiety.
Other compounds useful in treating psychotic disorders are known. For example, European Patent Application 0281309 states that compounds of the formula ##STR2## wherein Ar, n, X and Y are as defined in that application, are useful in treating psychotic disorders. The novel compounds of the present invention, however, exhibit substantially greater neuroleptic activity than such known compounds.
SUMMARY OF THE INVENTION
The present invention relates to compounds of the formula ##STR3## wherein W.sup.1 is CR.sup.2 R.sup.3, W.sup.2 is CR.sup.4 R.sup.5, W.sup.3 is CR.sup.6 R.sup.7 and one of W.sup.1, W.sup.2 and W.sup.3 may be absent and wherein the broken line extending from W.sup.1 to W.sup.3 represents an optional double bond between either and W.sup.1 and W.sup.2 or W.sup.2 and W.sup.3, in which case two of R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are absent; and wherein X.sup.1 is hydrogen, halogen, (C.sub.1 -C.sub.4)-alkyl, (C.sub.1 -C.sub.4)alkoxy, nitro, cyano, trifluoromethyl, or pentafluoroethyl or X.sup.1 forms a heterocyclic ring with Y.sup.1 ; Y.sup.1 is hydrogen, (C.sub.1 -C.sub.4) alkyl, phenyl or substituted phenyl, wherein said substituted phenyl is substituted with one or more substituents that are independently selected from the group consisting of halogen, (C.sub.1 -C.sub.4) alkyl, nitro, cyano, (C.sub.1 -C.sub.4) alkoxy, trifluoromethyl or pentafluoroethyl, or Y.sup.1 forms a heterocyclic ring with X.sup.1 ; ##STR4## wherein B is selected from the group consisting of S, O and NY.sup.2 ; X.sup.2 is hydrogen, halogen, (C.sub.1 -C.sub.4) alkyl, (C.sub.1 -C.sub.4) alkoxy nitro cyano trifluoromethyl or pentafluoroethyl, or X.sup.2 forms a heterocyclic ring with Y.sup.2 ; Y.sup.2 is hydrogen, (C.sub.1 -C.sub.4) alkyl, phenyl or substituted phenyl, wherein said substituted phenyl is substituted with one or more substituents that are independently selected from the group consisting of halogen, (C.sub.1 -C.sub.4) alkyl, (C.sub.1 -C.sub.4) alkoxy, nitro, cyano, trifluoromethyl or pentafluoro ethyl, or Y.sup.2 forms a heterocyclic ring with X.sup.2, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are independently selected from the group consisting of hydrogen and lower alkyl or any two of R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 taken together with the carbon or carbons to which they are attached form a (C.sub.3 -C.sub.7) saturated or unsaturated carbocyclic ring; and Z is (C.sub.1 -C.sub.6)alkyl, branched (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkenyl or branched (C.sub.1 -C.sub.6)alkenyl.
The present invention also relates to the pharmaceutically acceptable acid addition salts of the compounds of formula I. Such pharmaceutically acceptable acid addition salts include, but are not limited to the respective salts of acetic, malic, citric, fumaric, sulfuric, hydrochloric, hydrobromic, hydroiodic, sulfonic such as methanesulfonic and p-toluenesulfonic, and related acids.
Preferred compounds of the invention are: )-quinolinone hydrochloride hemihydrate, etrahydro-2(1H) -quinolinone hydrochloride hydrate, hydro-2(1H)-quinolinone hydrochloride hydrate, hydro-2(1H)-quinolinone hydrochloride hydrate, ethyl)-1,2,3,4-tetrahydro-2(1H) -quinolinone quarterhydrate, ethyl-2(1H)-quinolinone, -1-benzazepin-2-one, dro-2(1H)-quinolinone, and etrahydro(2(1H)-quinoline.
Specific compounds of the invention are: ifluoromethyl-2(1H)-quinolinone, 3,4-tetrahydro-2(1H)-quinolinone hydrochloride hydrate, thyl-7-trifluoromethyl-2(1H)-quinolinone, dimethyl-2(1H)-quinolinone, dimethyl-2(1H)-quinolinone, spiro[cyclopentane-1,4'-quinoline]-2'-one, -spiro[cyclopropane-1,4'-quinoline]-2'-one, ydro-4-methyl-2(1H)-quinolinone, ydro-4-methyl-2(1H) -quinolinone, ydro-4-methyl-2(1H)-quinolinone, loro-2H-1-benzazepin-2-one, and dimethyl-2H-1-benzazepin-2-one.
The comp
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Bond Robert T.
Butterfield Garth
Ginsburg Paul
Pfizer Inc
Richardson Peter C.
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