2-(1-Piperazinyl)-2,4,6-cycloheptatrien-1-one derivatives

Claim 2

A compound of the formula ##STR3## in which R 1 represents a substituent at positions 3, 4, 5, 6 or 7 of the 2,4,6-cycloheptatrien-1-one ring and is selected from hydrogen, halo, lower alkyl, lower alkoxy, trifluoromethyl, or 1-oxo(lower)alkylamino; R 2 is hydrogen or lower alkyl having one to three carbon atoms; and R 3 is hydrogen, phenyl, lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl, lower alkoxycarbonyl, 1-oxo(lower)alkyl, cyclo(lower)alkyl substituted with a lower alkyl; lower alkenyl substituted with phenyl; phenyl mono-, di or trisubstituted with lower alkyl, halo, lower alkoxy, hydroxy or trifluoromethyl; 2-(4,5-dihydro-2-oxazolyl)benzoyl, 2,3-dihydro-8-oxo-cyclohepta [b]furan-2-ylmethyl, 1-oxo-2,4,6-cycloheptatrien-2-yl, 2-(acetylamino)ethyl, 2,3-diacetyloxypropyl, 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyl or 5-methyl-2,4-imidazolidinedione-5-ylmethyl; or a therapeutically acceptable acid solution salt thereof.

Claim 3

A compound of claim 1 in which R 1 is hydrogen; R 2 is hydrogen or lower alkyl having one to three carbon atoms; and R 3 is hydrogen, phenyl, lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl, alkoxycarbonyl, 1-oxo(lower)alkyl, cyclo(lower)alkyl substituted with a lower alkyl; lower alkenyl substituted with phenyl; phenyl mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, hydroxy or trifluoromethyl; 2-(4,5-dihydro-2-oxazolyl)benzoyl, 2,3-dihydro-8-oxo-cyclohepta furan-2-ylmethyl, 1-oxo-2,4,6-cycloheptatrien-2-yl, 2-(acetylamino)ethyl, 2,3-diacetyloxypropyl, 2-(1,3-dihydro-1,3-dioxo-2H-iosindol-2-yl)ethyl, or 5-methyl-2,4-imidazolidinedione-5-ylmethyl; or a therapeutically acceptable acid addition salt thereof.

Claim 4

A compound of claim 1 in which R 1 is hydrogen; R 2 is hydrogen or methyl; and R 3 is hydrogen, phenyl, lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl, lower alkoxycarbonyl, 1-oxo(lower)alkyl, cyclo(lower)alkyl substituted with a lower alkyl; phenyl monosubstituted with lower alkyl, halo or trifluoromethyl; 2-(4,5-dihydro-2-oxazolyl)benzoyl, 1-oxo-2,4,6-cycloheptatrien-2-yl, 2-(acetylamino)ethyl, 2,3-diacetyloxypropyl, 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyl or 5-methyl-2,4-imidazolidinedione-5-ylmethyl; or a therapeutically acceptable acid addition salt thereof.

Claim 5

A compound of claim 1 in which R 1 and R 2 are hydrogen; and R 3 Is hydrogen, lower alkyl, lower alkenyl or lower alkoxycarbonyl; or a therapeutically acceptable acid addition thereof.

Claim 6

2-(4-Methyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is methyl.

Claim 7

2-[4-(2-Methylphenyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 2-methylphenyl.

Claim 8

2-[4-(4-Chlorophenyl)-2-methyl-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 is hydrogen, R 2 is 2-methy and R 3 is 4-chlorophenyl.

Claim 9

4-(2-Oxo-3,5,7-cycloheptatrien-1-yl)-1-piperazine carboxylic acid ethyl ester, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is ethoxycarbonyl.

Claim 10

2,2'-(1,4-Piperazinidyl)-bis-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 1-oxo-2,4,6-cycloheptatrien-2-yl.

Claim 11

2-(1-Piperazinyl)-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 , R 2 and R 3 are hydrogen.

Claim 12

2-[4-(2-Propenyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 2-proponyl.

Claim 13

1,3-Dihydro-2-[4-(2-oxo-3,5,7-cycloheptatrien-1-yl)ethyl]-2H-isoindol-1,3-dione, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyl.

Claim 14

2-[4-[2-(4,5-Dihydro-2-oxazolyl)benzoyl]-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 2-(4,5-dihydro-2-oxazolyl)benzoyl.

Claim 15

2-[4-(2-Propynyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 2-propynyl.

Claim 16

2-[4-(1,1-Dimethylethyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 1,1-dimethylethyl.

Claim 17

7-Bromo-2-(4-methyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 is 7-bromo, R 2 is hydrogen and R 3 is methyl.

Claim 18

5-Acetylamino-2-(4-methyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 is 5-acetylamino, R 2 is hydrogen and R 3 is methyl.

Claim 19

2-[4-(1-Methylethyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 1-methylethyl.

Claim 20

2-(4-Ethyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is ethyl.

Claim 21

2-(4-Propyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is propyl.

Claim 22

2-[4-(1-Methylpropyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 1-methylpropyl.

Claim 23

2-(2-Cyclopentyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is cyclopentyl.

Claim 24

2-(4-Acetyl-1-piperazinyl)-2,4,6-cycloheptatrien-4-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is acetyl.

Claim 25

5-Methyl-5-[[4-(2-oxo-3,5,7-cycloheptatrien-1-yl)-1-piperazinyl]methyl]-2,4-imidazolidinedione, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 5-methyl-2,4-imidazolinedione-5-ylmethyl.

Claim 26

N-[2-[4-(2-Oxo-3,5,7-cycloheptatrien-1-yl)-1-piperazinyl]ethyl]acetamide, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 2-(acetylamino)ethyl.

Claim 27

2-[4-(2,3-Diacetyloxypropyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 2,3-diacetyloxypropyl.

Claim 28

2-(4-Phenyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is phenyl.

Claim 29

2-(4-Cyclopropyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is cyclopropyl.

Claim 30

2-[4-(2-Methyl-2-propenyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 2-methyl-2-propenyl.

Claim 31

2-[4-(3-Trifluoromethylphenyl)-1-piperazinyl]-2,4,6-cycloheptatrien-1one, a compound of claim 1 wherein R 1 and R 2 are hydrogen and R 3 is 3-trifluoromethylphenyl.

Claim 32

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 ##STR4## in which R 1 represents a substituent at positions 3, 4, 5, 6 or 7 of the 2,4,6-cycloheptatrien-1-one ring and is selected from hydrogen, halo, lower alkyl, lower alkoxy, trifluoromethyl, or 1-oxo(lower)alkylamino; R 2 is hydrogen or lower alkyl having one to three carbon atoms; and R 3 is hydrogen, phenyl, lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl, lower alkoxycarbonyl, 1-oxo(lower)-alkyl, cyclo(lower)alkyl substituted with a lower alkyl; lower alkenyl substituted with phenyl; phenyl mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, hydroxy or trifluoromethyl; 2-(4,5-dihydro-2-oxazolyl)benzoyl, 2,3-dihydro-8-oxo-cyclohepta[b]furan-2-ylmethyl, oxo-2,4,6-cycloheptatrien-2-yl, 2-(acetylamino)ethyl, 2,3-diacetyloxypropyl, 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyl or 5-methyl-2,4-imidazolidinedione-5-ylmethyl; or a therapeutically acceptable acid addition salt thereof, and a pharmaceutically acceptable carrier therefor.

Claim 33

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 ##STR4## in which R 1 represents a substituent at positions 3, 4, 5, 6 or 7 of the 2,4,6-cycloheptatrien-1-one ring and is selected from hydrogen, halo, lower alkyl, lower alkoxy, trifluoromethyl, or 1-oxo(lower)alkylamino; R 2 is hydrogen or lower alkyl having one to three carbon atoms; and R 3 is hydrogen, phenyl, lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl, lower alkoxycarbonyl, 1-oxo(lower)-alkyl, cyclo(lower)alkyl substituted with a lower alkyl; lower alkenyl substituted with phenyl; phenyl mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, hydroxy or trifluoromethyl; 2-(4,5-dihydro-2-oxazolyl)benzoyl, 2,3-dihydro-8-oxo-cyclohepta[b]furan-2-ylmethyl, oxo-2,4,6-cycloheptatrien-2-yl, 2-(acetylamino)ethyl, 2,3-diacetyloxypropyl, 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyl or 5-methyl-2,4-imidazolidinedione-5-ylmethyl; or a therapeutically acceptable acid addition salt thereof, and a pharmaceutically acceptable carrier therefor.

Claim 34

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 31.

Claim 35

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 31, 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 36

The method of claim 33 wherein the composition of claim 31, and said agent are administered sequentially or simultaneously.

Claim 37

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 ##STR5## in which R 1 represents a substituent at positions 3, 4, 5, 6 or 7 of the 2,4,6-cycloheptatrien-1-one ring and is selected from hydrogen, halo, lower alkyl, lower alkoxy, trifluoromethyl, or 1-oxo(lower)alkylamino; R 2 is hydrogen or lower alkyl having one to three carbon atoms; and R 3 is hydrogen, phenyl, lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl, lower alkoxycarbonyl, 1-oxo(lower)alkyl, cyclo(lower)alkyl substituted with a lower alkyl; lower alkenyl substituted with phenyl; phenyl mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, hydroxy or trifluoromethyl; 2-(4,5-dihydro-2-oxazolyl)benzoyl, 2,3-dihydro-8-oxo-cyclohepta[b]furan-2-ylmethyl, 1-oxo-2,4,6-cycloheptatrien-2-yl, 2-(acetylamino)ethyl, 2,3-diacetyloxypropyl, 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyl or 5-methyl-2,4-imidazolidinedione-5-ylmethyl; or a therapeutically acceptable acid addition salt thereof, and an agent selected from bromocriptine, lergotrile, levodopa, combination of levodopa and carbidopa, L-prolyl-L-leucylglycinamide and L-prolyl-N-methyl-D-leucylglycinamide.

Claim 38

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 ##STR5## in which R 1 represents a substituent at positions 3, 4, 5, 6 or 7 of the 2,4,6-cycloheptatrien-1-one ring and is selected from hydrogen, halo, lower alkyl, lower alkoxy, trifluoromethyl, or 1-oxo(lower)alkylamino; R 2 is hydrogen or lower alkyl having one to three carbon atoms; and R 3 is hydrogen, phenyl, lower alkyl, lower alkenyl, lower alkynyl, cyclo(lower)alkyl, lower alkoxycarbonyl, 1-oxo(lower)alkyl, cyclo(lower)alkyl substituted with a lower alkyl; lower alkenyl substituted with phenyl; phenyl mono-, di- or trisubstituted with lower alkyl, halo, lower alkoxy, hydroxy or trifluoromethyl; 2-(4,5-dihydro-2-oxazolyl)benzoyl, 2,3-dihydro-8-oxo-cyclohepta[b]furan-2-ylmethyl, 1-oxo-2,4,6-cycloheptatrien-2-yl, 2-(acetylamino)ethyl, 2,3-diacetyloxypropyl, 2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyl or 5-methyl-2,4-imidazolidinedione-5-ylmethyl; or a therapeutically acceptable acid addition salt thereof, and an agent selected from bromocriptine, lergotrile, levodopa, combination of levodopa and carbidopa, L-prolyl-L-leucylglycinamide and L-prolyl-N-methyl-D-leucylglycinamide.