2-(4-Substituted alkyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one derivatives

Claim 2

A compound of the formula ##STR5## in which Alk is a divalent alkyl having one to six carbon atoms; R 1 is hydrogen or lower alkyl having one to three carbon atoms; and R 2 is lower alkoxy, cyano, aminocarbonyl, lower alkoxycarbonyl, cyclo(lower)alkyl, phenyl, phenoxy, hydroxy(lower)alkoxy, 3-indolyl, 1-oxo-2,4,6-cycloheptatrien-2-yl-amino, 1-imidazol-4-yl, 1-oxo(lower)alkoxy, acetylthio, phenyl mono-, di or trisubstituted with lower alkyl, halo, lower alkoxy, hydroxy or trifluoromethyl, or phenoxy mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, acetylamino, hydroxy or trifluoromethyl; or a therapeutically acceptable acid addition salt thereof.

Claim 3

A compound of claim 1 in which Alk is a divalent alkyl having one to six carbon atoms; R 1 is hydrogen; and R 2 is lower alkoxy, cyano, aminocarbonyl, lower alkoxycarbonyl, cyclo(lower)alkyl, phenyl, phenoxy, hydroxy(lower)alkoxy, 3-indolyl, 1-oxo-2,4,6-cycloheptatrien-2-yl-amino, 1H-imidazol-4-yl, 1-oxo(lower)alkoxy, acetylthio, phenyl mono-, di- or trisubstituted with lower alkoxy or hydroxy, or phenyl mono-, di- or trisubstituted with lower alkyl, halo or acetylamino; or a therapeutically acceptable acid addition salt thereof.

Claim 4

A compound of claim 1 in which Alk is a divalent alkyl having one to three carbon atoms; R 1 is hydrogen; and R 2 is lower alkoxy, cyano, aminocarbonyl, lower alkoxycarbonyl cyclo(lower)alkyl, phenyl, phenoxy, hydroxy(lower)alkoxy, 3-indolyl, 1-oxo-2,4,6-cycloheptatrien-2-yl-amino, 1H-imidazol-4-yl, 1-oxo(lower)alkoxy, acetylthio, phenyl mono- or disubstituted with lower alkoxy or hydroxy, or phenoxy monosubstituted with lower alkyl, halo or acetylamino; or a therapeutically acceptable acid addition salt thereof.

Claim 5

A compound of claim 1 in which Alk is a divalent alkyl having one or two carbon atoms; R 1 is hydrogen; and R 2 is lower alkoxy, cyano, 1-oxo(lower)alkoxy, or phenyl mono- or disubstituted with lower alkoxy or hydroxy; or a therapeutically therapeutically acid addition salt thereof.

Claim 6

2-[4-(Phenylmethyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 , R 1 is hydrogen and R 2 is phenyl.

Claim 7

N,4-Bis-(2-oxo-3,5,7-cycloheptatrien-1-yl)-1-piperazine-ethanamine, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is 1-oxo-2,4,6-cycloheptatrien-2-ylamino.

Claim 8

4-(2-Oxo-3,5,7-cycloheptatrien-1-yl)-1-piperazine acetic acid, ethyl ester, a compund of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is ethoxycarbonyl.

Claim 9

4-(2-Oxo-3,5,7-cycloheptatrien-1-yl)-1-piperazine-acetonitrile, a compound of claim 1 wherein Alk is CH 2 , R 1 is hydrogen and R 2 is cyano.

Claim 10

2-[4-(2-(Phenoxyethyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 Ch 2 , R 1 is hydrogen and R 2 is phenoxy.

Claim 11

2-[4-(2-Ethoxyethyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is ethoxy.

Claim 12

2-[4-[2-(2-Hydroxyethoxy)ethyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is 2-hydroxyethoxy.

Claim 13

2-[4-(2-phenylethyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is phenyl.

Claim 14

2-[4-[2-(3,4-Dimethoxyphenyl)ethyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is 3,4-dimethoxyphenyl.

Claim 15

2-[4-[2-(3,4-Dihydroxyphenyl)ethyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is 3,4-dihydroxyphenyl.

Claim 16

4-(2-Oxo-3,5,7-cycloheptatrien-1-yl)-1-piperazine-acetamide, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is aminocarbonyl.

Claim 17

2-[4-[2-(Acetyloxy)ethyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is acetyloxy.

Claim 18

2,2-Dimethylpropanoic acid, 2-[4-(2-oxo-3,5,7-cycloheptatrien-1-yl)-1-piperazinyl]ethyl ester, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is 2,2-dimethyl-1-oxopropoxy.

Claim 19

2-[4-[2-[4-(1,1-Dimethylethyl)phenoxy]ethyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is 4-(1,1-dimethylethyl)phenoxy.

Claim 20

2-[4-[2-(4-Chlorophenoxy)ethyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is 4-chlorophenoxy.

Claim 21

2-[4-[2-[4-(Acetylamino)phenoxy]ethyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is 4-acetylamino)phenoxy).

Claim 22

2-[4-[2-(3-Indolyl)ethyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is 3-indolyl.

Claim 23

2-[4-[2-(1H-Imidazol-4-yl)ethyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is 1H-imidazol-4-yl.

Claim 24

2-[4-[2-(Acetylthio)ethyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is acetylthio.

Claim 25

2-[4-[2-(4-Fluorophenyl)ethyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein Alk is CH 2 CH 2 , R 1 is hydrogen and R 2 is 4-fluorophenyl.

Claim 26

A pharmaceutical composition, for stimulating dopamine receptors in a mammal in need thereof, which comprises an effective dopamine receptor stimulating amount of a compound of the formula ##STR6## in which Alk is a divalent alkyl having one to six carbon atoms; R 1 is hydrogen or lower alkyl having one to three carbon atoms; and R 2 is lower alkoxy, cyano, aminocarbonyl, lower alkoxycarbonyl, cyclo(lower)alkyl, phenyl, phenoxy, hydroxy(lower)alkoxy, 3-indolyl, 1-oxo-2,4,6-cycloheptatrien-2-yl-amino, 1H-imidazol-4-yl, 1-oxo(lower)alkoxy, acetylthio, phenyl mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, hydroxy or trifluoromethyl, or phenyl mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, acetylamino, hydroxy or trifluoromethyl; or a therapeutically acceptable acid addition salt thereof, and a pharmaceutically acceptable carrier therefor.

Claim 27

A pharmaceutical composition, for stimulating dopamine receptors in a mammal in need thereof, which comprises an effective dopamine receptor stimulating amount of a compound of the formula ##STR6## in which Alk is a divalent alkyl having one to six carbon atoms; R 1 is hydrogen or lower alkyl having one to three carbon atoms; and R 2 is lower alkoxy, cyano, aminocarbonyl, lower alkoxycarbonyl, cyclo(lower)alkyl, phenyl, phenoxy, hydroxy(lower)alkoxy, 3-indolyl, 1-oxo-2,4,6-cycloheptatrien-2-yl-amino, 1H-imidazol-4-yl, 1-oxo(lower)alkoxy, acetylthio, phenyl mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, hydroxy or trifluoromethyl, or phenyl mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, acetylamino, hydroxy or trifluoromethyl; or a therapeutically acceptable acid addition salt thereof, and a pharmaceutically acceptable carrier therefor.

Claim 28

A method of stimulating dopamine receptors in a mammal in need thereof, which comprises administering to said mammal and effective dopamine receptor stimulating amount of a composition of claim 25.

Claim 29

A method of stimulating dopamine receptors in a mammal in need thereof, which comprises administering to said mammal an effective dopamine receptor stimulating amount of a composition of claim 25, in combination with an effective amount of an agent selected from bromocriptine, lergotrile, levodopa, combination of levodopa and carbidopa, L-prolyl-L-leucylglycinamide and L-prolyl-N-methyl-D-leucylglycinamide.

Claim 30

The method of claim 27 wherein the composition of claim 25, and said agent are administered sequentially or simultaneously.

Claim 31

A pharmaceutical composition for stimulating dopamine receptors in a mammal in need thereof comprising an effective dopamine receptor stimulating amount of a compound of the formula ##STR7## in which Alk is a divalent alkyl having one to six carbon atoms; R 1 is hydrogen or lower alkyl having one to three carbon atoms; and R 2 is lower alkoxy, cyano, aminocarbonyl, lower alkoxycarbonyl, cyclo(lower)alkyl, phenyl, phenoxy, hydroxy(lower)alkoxy, 3-indolyl, 1-oxo-2,4,6-cycloheptatrien-2-yl-amino, 1H-imidazol-4-yl, 1-oxo(lower)alkoxy, acetylthio, phenyl mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, hydroxy or trifluoromethyl, or phenoxy mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, acetylamino, hydroxy or trifluoromethyl; or a therapeutically acceptable acid addition salt thereof, and an agent selected from bromocriptine, lergotrile, levodopa, combination of levodopa and carbidopa, L-propyl-L-leucylglycinamide and L-propyl-N-methyl-D-leucylglycinamide.

Claim 32

A pharmaceutical composition for stimulating dopamine receptors in a mammal in need thereof comprising an effective dopamine receptor stimulating amount of a compound of the formula ##STR7## in which Alk is a divalent alkyl having one to six carbon atoms; R 1 is hydrogen or lower alkyl having one to three carbon atoms; and R 2 is lower alkoxy, cyano, aminocarbonyl, lower alkoxycarbonyl, cyclo(lower)alkyl, phenyl, phenoxy, hydroxy(lower)alkoxy, 3-indolyl, 1-oxo-2,4,6-cycloheptatrien-2-yl-amino, 1H-imidazol-4-yl, 1-oxo(lower)alkoxy, acetylthio, phenyl mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, hydroxy or trifluoromethyl, or phenoxy mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, acetylamino, hydroxy or trifluoromethyl; or a therapeutically acceptable acid addition salt thereof, and an agent selected from bromocriptine, lergotrile, levodopa, combination of levodopa and carbidopa, L-propyl-L-leucylglycinamide and L-propyl-N-methyl-D-leucylglycinamide.