RU2002110106A

RU2002110106A - New derivatives of pyrimidine-2, 4,6-triones, a method for their preparation and pharmaceutical agents containing these compounds

Info

Publication number: RU2002110106A
Application number: RU2002110106/04A
Authority: RU
Inventors: Франк ГРАМС; Ханс-Вили КРЕЛЛЬ; Герберт ЛАЙНЕРТ; Эрнесто Мента; Герд ЦИММЕРМАНН
Original assignee: Ф.Хоффманн-Ля Рош Аг
Priority date: 1999-10-01
Filing date: 2000-09-29
Publication date: 2003-11-20

Claims

1. The compounds of formula I

where R ₁ denotes a phenoxy group in which the phenyl residue can be substituted by one or more halogen atoms, hydroxy, C ₁ -C ₆ alkoxy, C ₁ -C ₆ alkyl, cyano or nitro groups, and

R ₂ is pyrimidine, pyrazine or its N-oxide or phenyl substituted with —SO ₂ NR ₃ R ₄ ,

where R ₃ and R ₄ , which may be the same or different, denote a hydrogen atom, a straight-chain or branched C ₁ -C ₆ alkyl, which may be substituted one or more times by the group OH, N (CH ₃ ) ₂ or which may be interrupted by an atom oxygen, or represents COR ₅ , where R ₅ denotes an alkyl group that may be substituted with NH ₂ .

2. The compounds according to claim 1 of formula I,

in which R ₁ denotes a phenoxy radical substituted one or more times by chlorine, bromine, methyl or tert-butyl atoms.

3. The compounds according to claim 1 of formula I, in which R ₃ denotes a hydrogen atom, and R ₄ denotes a hydrogen atom, —CH ₂ CH ₂ OH; -CH ₂ CH ₂ -N (CH ₃ ) ₂ ; -CH ₂ -CH (OH) -CH ₂ OH; -CH- (CH ₂ OH) ₂ ; —CH ₂ —CH ₂ —O — CH ₂ CH ₂ —O — CH ₂ CH ₂ OH or —C (CH ₂ OH) ₃ .

4. The compounds according to claim 1 of formula I, selected from a series including:

5- [4- (4-chlorophenoxy) phenyl] -5- (4-pyrimidin-2-ylpiperazine) pyrimidine-2,4,6-trion,

5- [4- (4-chlorophenoxy) phenyl] -5- (2,3,5,6-tetrahydro [1,2 ’] bipyrazinyl-4-yl) pyrimidine-2,4,6-trion,

5- [4- (3,4-dichlorophenoxy) phenyl] -5- (4-pyrimidin-2-ylpiperazin-1-yl) pyrimidine-2,4,6-trion,

5- [4- (3,4-dichlorophenoxy) phenyl] -5- (2,3,5,6-tetrahydro [1,2 ’] bipyrazinyl-4-yl) pyrimidine-2,4,6-trion,

5- [4- (4-bromophenoxy) phenyl] -5- (4-pyrimidin-2-ylpiperazin-1-yl) pyrimidine-2,4,6-trion,

4- {4-5- [4- (4-chlorophenoxy) phenyl] -2,4,6-trioxohexahydropyrimidin-5-ylpiperazin-1-yl} -N- (2-hydroxyethyl) benzenesulfonamide,

4- {4-5- [4- (4-bromophenoxy) phenyl] -2,4,6-trioxohexahydropyrimidin-5-ylpiperazin-1-yl} benzenesulfonamide,

4- {4-5- [4- (4-bromophenoxy) phenyl] -2,4,6-trioxohexahydropyrimidin-5-ylpiperazin-1-yl} -N- (2-dimethylaminoethyl) benzenesulfonamide,

4- {4-5- [4- (4-chlorophenoxy) phenyl] -2,4,6-trioxohexahydropyrimidin-5-ylpiperazin-1-yl} benzenesulfonamide,

4- {4-5- [4- (4-chlorophenoxy) phenyl] -2,4,6-trioxohexahydropyrimidin-5-ylpiperazin-1-yl} -N, N-bis (2-hydroxyethyl) benzenesulfonamide,

N- (2,3-dihydroxypropyl) -4-4- [2,4,6-trioxo-5- (4-phenoxyphenyl) hexahydropyrimidin-5-yl] piperazin-1-ylbenzenesulfonamide,

N- (2-hydroxy-1-hydroxymethylethyl) -4-4- [2,4,6-trioxo-5- (4-phenoxyphenyl) hexahydropyrimidin-5-yl] piperazin-1-ylbenzenesulfonamide,

N-2- [2- (2-hydroxyethoxy) ethoxy] ethyl-4-4- [2,4,6-trioxo-5- (4-phenoxyphenyl) hexahydropyrimidin-5-yl] piperazin-1-ylbenzenesulfonamide,

N- (2-hydroxy-1,1-bishydroxymethylethyl) -4-4- [2,4,6-trioxo-5- (4-phenoxyphenyl) hexahydropyrimidin-5-yl] piperazin-1-ylbenzenesulfonamide,

4- {4-5- [4- (4-chlorophenoxy) phenyl] -2,4,6-trioxohexahydropyrimidin-5-ylpiperazin-1-yl} -N- (2-hydroxy-1,1-bishydroxymethylethyl) benzenesulfonamide,

N- (2-oxo [1,3] dioxolan-4-ylmethyl) -4-4- [2,4,6-trioxo-5- (4-phenoxyphenyl) hexahydropyrimidin-5-yl] piperazin-1-ylbenzenesulfonamide.

5. Pharmaceutical compositions, as an active ingredient, comprising a compound according to claims 1-4 in a mixture with pharmaceutically acceptable excipients or diluents.

6. The use of compounds according to claims 1-4 for the preparation of a medicament exhibiting inhibitory activity against metalloproteinases.

7. The use of compounds according to claim 6, exhibiting antitumor and / or antimetastatic activity.