Substituted piperazine derivatives as mtp inhibitors

Substituted piperazine derivatives of general formula

• 6
• n denotes the number 2, 3, 4 or 5,
• X denotes a carbon-carbon bond, an oxygen atom, a methylene, ethylene, imino or N-(C1-3-alkyl)-imino group,
• Ya denotes a carbonyl or sulphonyl group,
• Yb denotes the group —(CH2)m—, wherein m denotes the number 2 or 3 and wherein a hydrogen atom may be replaced by a C1-3-alkyl group or a methylene group linked to a nitrogen atom may be replaced by a carbonyl group,
• Ra denotes a C1-6-alkoxy-, phenyl-C1-3-alkoxy or amino group, wherein the amino group may be mono- or disubstituted by C1-3-alkyl-, phenyl-C1-4-alkyl or phenyl groups and the substituents may be identical or different,
• a phenyl-, naphthyl, tetrahydronaphthyl, phenoxy or heteroaryl group, a C1-9-alkyl group optionally substituted by a hydroxy, C1-3-alkoxy, C1-4 alkoxycarbonyl or C1-4-alkyl-carbonyloxy group, which may be substituted in the alkyl moiety by a C1-3-alkyl group, by one or two phenyl groups, by a naphthyl, fluorenyl, phenoxy, heteroaryl or C3-7-cycloalkyl group, or a C3-7-cycloalkyl group substituted by a phenyl group,
• a phenylcarbonyl, naphthylcarbonyl, tetrahydronaphthylcarbonyl, phenoxycarbonyl or heteroarylcarbonyl group, a C1-9-alkylcarbonyl group, which may be substituted in the alkyl moiety by one or two phenyl groups, by a naphthyl, fluorenyl, phenoxy, heteroaryl or C3-7-cycloalkyl group, or a C3-7-cycloalkylcarbonyl group substituted by a phenyl group,
• wherein all the phenyl, naphthyl and heteroaryl moieties mentioned under Ra hereinbefore may be substituted by the groups R1 and R2, wherein
• R1 denotes a hydrogen, fluorine, chlorine or bromine atom, a cyano, C1-3-alkyl, C2-4-alkenyl, phenyl, hydroxy, C1-4-alkoxy, phenyl-C1-3-alkoxy, carboxy, C1-3-alkoxycarbonyl, aminocarbonyl, C1-3-alkylaminocarbonyl, N,N-di-(C1-3-alkyl)-aminocarbonyl, nitro, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, phenyl-C1-3-alkylamino, N-(C1-3-alkyl)-phenyl-C1-3-alkylamino, C1-3-alkylcarbonylamino, N-(C1-3-alkyl) —C1-3-alkylcarbonylamino, C1-3-alkylsulphonylamino or N-(C1-3-alkyl) —C1-3-alkyl-sulphonylamino group and
• R2 denotes a hydrogen, fluorine, chlorine or bromine atom, a C1-3-alkyl, hydroxy or C1-4-alkoxy group, wherein in the abovementioned alkyl and alkoxy moieties of the groups R1 and R2 the hydrogen atoms may be wholly or partially replaced by fluorine atoms, or
• R1 and R2 together denote a methylenedioxy group,
• or wherein all the phenyl moieties mentioned above under Ra may be substituted by three chlorine or bromine atoms or by three to five fluorine atoms,
• Rb denotes a carboxy, C1-6-alkoxycarbonyl, C1-6-alkoxycarbonyl-C1-3-alkylcarbonyl, C3-7-cycloalkoxycarbonyl or phenyl-C1-3-alkoxycarbonyl group or a R3NR4—CO group wherein
• R3 and R4, which may be identical or different, denote hydrogen atoms, C1-6-alkyl groups wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms and the C1-3-alkyl moiety of a C1-3-alkylamino group may be substituted by a carboxy or C1-3-alkoxycarbonyl group or in the 2 or 3 position may also be substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, C1-3-cycloalkyl, pyridyl, pyridinyl-C1-3-alkyl, phenyl, naphthyl or phenyl-C1-3-alkyl groups, wherein the abovementioned phenyl groups may be substituted in each case by a fluorine, chlorine or bromine atom, by a C1-3-alkyl group wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms, by a hydroxy, C1-3-alkoxy, carboxy, C1-3-alkoxycarbonyl, aminocarbonyl, C1-3-alkylaminocarbonyl, N,N-di-(C1-3-alkyl)-aminocarbonyl or N,N-di-(C31-alkyl)-amino group, or
• R3 and R4 together with the nitrogen atom between them denote a 3- to 7-membered cycloalkyleneimino group, wherein the methylene group in the 4 position of a 6 or 7-membered cycloalkyleneimino group may additionally be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, imino or N-(C1-3-alkyl)-imino group,
• and Rc denotes a hydrogen atom or a C1-3-alkyl group,
• wherein the tricyclic group in the abovementioned general formula I may additionally be mono- or disubstituted by fluorine or chlorine atoms, by methyl or methoxy groups and the substituents may be identical or different,
• by the abovementioned heteroaryl groups is meant a 6-membered heteroaryl group, containing one, two or three nitrogen atoms, or
• a 5-membered heteroaryl group, containing an imino group optionally substituted by a C1-3-alkyl group, an oxygen or sulphur atom or
• an imino group optionally substituted by a C1-3-alkyl group and one or two nitrogen atoms or
• an oxygen or sulphur atom and a nitrogen atom,
• wherein a phenyl ring may be fused to the above-mentioned heteroaryl groups via a vinylene group,
• and wherein the carboxy group mentioned in the definition of the abovementioned groups may be replaced by a group which can be converted into a carboxy group in vivo or by a group which is negatively charged under physiological conditions,
• and all the abovementioned saturated alkyl and alkoxy moieties which contain more than 2 carbon atoms may be straight-chain or branched, unless stated otherwise,
• the isomers and salts thereof.