Claims for Patent: 8,349,840
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Summary for Patent: 8,349,840
| Title: | Piperazine-substituted benzothiophenes for treatment of mental disorders |
| Abstract: | The present invention provides a heterocyclic compound represented by the general formula (1): The compound of the present invention has a wide treatment spectrum for mental disorders including central nervous system disorders, no side effects and high safety. ##STR00001## |
| Inventor(s): | Yamashita; Hiroshi (Tokushima, JP), Ito; Nobuaki (Tokushima, JP), Miyamura; Shin (Tokushima, JP), Oshima; Kunio (Tokushima, JP), Matsubara; Jun (Tokushima, JP), Kuroda; Hideaki (Tokushima, JP), Takahashi; Haruka (Tokushima, JP), Shimizu; Satoshi (Tokushima, JP), Tanaka; Tatsuyoshi (Tokushima, JP) |
| Assignee: | Otsuka Pharmaceutical Co., Ltd. (Tokyo, JP) |
| Application Number: | 12/970,690 |
| Patent Litigation and PTAB cases: | See patent lawsuits and PTAB cases for patent 8,349,840 |
| Patent Claims: |
1. A pharmaceutical composition comprising a heterocyclic compound of the formula (1) or a salt thereof as an active ingredient and a pharmaceutically acceptable
carrier: ##STR00178## wherein ring Q represented by ##STR00179## represents ##STR00180## wherein ##STR00181## represents --NH--CH.sub.2--, --N.dbd.CH--, --CH.sub.2--NH-- or --CH.dbd.N--; and the carbon-carbon bond between the 3-position and 4-position
of the heterocyclic skeleton containing Z and Y represents a single bond or a double bond; the ring Q may have at least one substituent selected from the group consisting of a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a hydroxy
group, a lower alkoxy group, a halogenated lower alkyl group, an aryl group, an aryl lower alkyl group, an aryl lower alkoxy group, an arylcarbonyl group, a lower alkenyloxy group, a lower alkanoyl group, a lower alkanoyloxy group, a cycloalkyl group, a
cycloalkyl lower alkyl group, a halogen atom, a carbamoyl group which may have a lower alkyl group, a carboxy group, a lower alkoxycarbonyl group, an amino group which may have a lower alkanoyl group, a nitro group, a hydroxy lower alkyl group, an amino
lower alkyl group which may have a lower alkyl group, a thienyl group, a saturated 3- to 8-membered heteromonocyclic group containing 1 to 2 nitrogen atoms-substituted lower alkyl group and an oxo group; R.sub.2 represents a hydrogen atom or a lower
alkyl group; and A represents --O -A.sub.1- (wherein A.sub.1 represents an alkylene group which may be substituted with a hydroxy group (wherein the one oxygen atom may replace a carbon of the alkylene chain) or a lower alkenylene group) or a lower
alkylene group; provided that when A represents a lower alkylene group, the ring Q represents a bicyclic group selected from the group consisting of: ##STR00182## wherein the carbon-carbon-bond represents a single bond or a double bond.
2. A pharmaceutical composition comprising a heterocyclic compound or a salt thereof selected from the group of: (1) 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one, (2) 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-1H-quinolin-2-o- ne, (3) 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-3,4-dihydro-- 1H-quinolin-2-one, (4) 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-3,4-dihydro-1H-quino- lin-2-one, (5) 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1-methyl-3,4-dihydro- -1H-quinolin-2-one and (6) 6-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-3,4-dihydro-1H-quin- olin-2-one; or a salt thereof, as an active ingredient and a pharmaceutically acceptable carrier. 3. A pharmaceutical composition comprising a heterocyclic compound or a salt, thereof selected from the group of: (1) 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-3,4-dihydro-2H-isoq- uinolin-1-one (2) 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-2-methyl-3,4-dihydr- o-2H-isoquinolin-1-one, (3) 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-2-methyl-3,4-dihydro- -2H-isoguinolin-1-one, (4) 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-3,4-dihydro-2H-isoqu- inoline-1-one, (5) 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-2H-isoguinolin-1-on- e and (6) 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-2-methyl-2- H-iosquinolin-1-one; or a salt thereof, as an active ingredient and a pharmaceutically acceptable carrier. 4. A method for treating a central nervous system disorder selected from depression, endogenous depression, major depression, melancholy and refractory depression comprising administering a heterocyclic compound represented by the formula (1) or a salt thereof to a human or animal: ##STR00183## wherein ring Q represented by ##STR00184## represents ##STR00185## wherein ##STR00186## represents --NH--CH.sub.2--, --N.dbd.CH--, --CH.sub.2--NH-- or --CH.dbd.N--; and the carbon-carbon bond between the 3-position and 4-position of the heterocyclic skeleton containing Z and Y represents a single bond or a double bond; the ring Q may have at least one substituent selected from the group consisting of a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a hydroxy group, a lower alkoxy group, a halogenated lower alkyl group, an aryl group, an aryl lower alkyl group, an aryl lower alkoxy group, an arylcarbonyl group, a lower alkenyloxy group, a lower alkanoyl group, a lower alkanoyloxy group, a cycloalkyl group, a cycloalkyl lower alkyl group, a halogen atom, a carbamoyl group which may have a lower alkyl group, a carboxy group, a lower alkoxycarbonyl group, an amino group which may have a lower alkanoyl group, a nitro group, a hydroxy lower alkyl group, an amino lower alkyl group which may have a lower alkyl group, a thienyl group, a saturated 3- to 8-membered heteromonocyclic group containing 1 to 2 nitrogen atoms-substituted lower alkyl group and an oxo group; R.sub.2 represents a hydrogen atom or a lower alkyl group; and A represents --O-A.sub.1- (wherein A.sub.1 represents an alkylene group which may be substituted with a hydroxy group (wherein the one oxygen atom may replace a carbon of the alkylene chain) or a lower alkenylene group) or a lower alkylene group; provided that when A represents a lower alkylene group, the ring Q represents a bicyclic group selected from the group consisting of: ##STR00187## wherein the carbon-carbon-bond represents a single bond or a double bond. 5. The method according to claim 4, wherein the heterocyclic compound or a salt thereof is selected from the group of: (1) 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one, (2) 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-1H-quinolin-2-o- ne, (3) 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1- yl)propoxy]-3,4-dihydro-1H-quinolin-2-one, (4) 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-3,4-dihydro-1H-quino- lin-2-one, (5) 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1-methyl-3,4-dihydro- -1H-quinolin-2-one and (6) 6-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-3,4-dihydro-1H-quin- olin-2-one; or a salt thereof. 6. The method according to claim 4, wherein the heterocyclic compound or a salt thereof is selected from the group of: (1) 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-3,4-dihydro-2H-isoq- uinolin-1-one (2) 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-2-methyl-3,4-dihydr- o-2H-isoquinolin-1-one, (3) 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-2-methyl-3,4-dihydro- -2H-isoquinolin-1-one, (4) 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-3,4-dihydro-2H-isoqu- inoline-1-one, (5) 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-2H-isoquinolin-1-on- e and (6) 7-[3-(4-benzo(b)thiophen-4-yl-piperazin-1-yl)propoxy]-2-methyl-2- H-iosquinolin-1-one; or a salt thereof. |
