# US 5,350,747 A · Heteroaryl piperazine antipsychotic agents

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- Number: US 5,350,747 A
- Document ID: US5350747A
- Status: Granted
- Kind: A
- Application number: 07/836,019
- Filed: 1992-02-20
- Granted: 1994-09-27
- Earliest claimed: 1992-02-20
- Assignees: Pfizer Inc.
- Inventors: Harry R. Howard
- Web page: https://patentgrep.com/patent/US5350747A

## CPC

- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Compounds of the formula ##STR1## and pharmaceutical compositions comprising them, wherein R.sup.1, Z, X, W and Y are as defined below. The compounds are useful in the treatment of psychosis and anxiety.

## Claims

### Claim 1

A compound having the formula ##STR6## 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 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; 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, (C.sub.1 -C.sub.4) alkoxy, nitro, cyano, trifluoromethyl or pentafluoroethyl, or when X.sup.1 is attached to the carbon atom ortho to the carbon atom to which N-Y.sup.1 is attached then X.sup.1 and Y.sup.6 together may optionally form a saturated heterocyclic ring selected from pyrrolidine, piperidine, perhyddroazepine, 3-oxazolane and morpholine;
R.sup.1 is ##STR7## 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; 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 trifluoroethyl; 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,
and the pharmaceutically acceptable salts thereof.

### Claim 2 (depends on 1)

A compound according to claim 1, with the proviso that when Y.sup.1 is hydrogen and W.sup.3 is absent, then the heterocyclic ring carbons of W.sup.1 and W.sup.2 are connected by a carbon-carbon single bond.

### Claim 3 (depends on 1)

A compound according to claim 1, wherein Y.sup.1 is hydrogen, W.sup.3 is absent and the heterocyclic ring carbons of W.sup.1 and W.sup.2 are connected by a carbon-carbon double bond.

### Claim 4 (depends on 1)

A compound according to claim 1, said compound being selected from the group consisting of:
6-(2-(4-(1,2-benzisothiazol-3-yl)piperazinyl)ethyl)-1,2,3,4-tetrahydro-2(1H )-quinolinone hydrochloride hemihydrate,
4(R,S)-methyl-6-(2-(4-(1,2-benzisothiazol-3-yl)piperazinyl)ethyl)-1,2,3,4-t etrahydro-2(1H)-quinolinone hydrochloride hydrate,
4S-methyl-6-(2-(4-(1,2-benzisothiazol-3-yl)piperazinyl)ethyl)-1,2,3,4-tetra hydro-2(1H)-quinolinone hydrochloride hydrate,
4R-methyl-6-(2-(4-(1,2-benzisothiazol-3-yl)piperazinyl)ethyl)-1,2,3,4 -tetrahydro-2(1H)-quinolinone hydrochloride hydrate,
7-chloro-6-(2-(4-(1,2-benzisothiazol-3-yl)piperazinyl)ethyl)-1,2,3,4-tetrah ydro-2(1H)-quinolinone quarterhydrate,
6-(3-(4-(1,2-benzisothiazol-3-yl)piperazinyl)propyl)-1,2,3,4-tetrahydro-4-m ethyl-2(1H)-quinolinone,
7-(2-(4-(1,2-benzisothiazol-3-yl)-piperazinyl)ethyl)-1,3,4,5-tetrahydro-2H- 1-benzazepin-2-one,
1-ethyl-6-(2-(4-(1,2-benzisothiazol-3-yl)piperazinyl)ethyl)-1,2,3,4-tetrahy dro-2(1H)-quinolinone, and
4,4-dimethyl-6-(2-(4-(1,2-benzisothiazol-3-yl)piperazinyl)ethyl)-1,2,3,4-te trahydro-2(1H)-quinoline.

### Claim 5 (depends on 1)

A pharmaceutical composition for the treatment or prevention of psychosis and anxiety, comprising an amount of a compound according to claim 1 effective in treating or preventing psychosis or anxiety.

### Claim 6 (depends on 1)

A method for the treatment or prevention of psychosis or anxiety, comprising administering to a person in need of said treatment or prevention a compound according to claim 1 in an amount effective to treat or prevent psychosis or anxiety.