US 6,586,613 B1 · Substituted tetrahydronaphthaline and analogous compounds

Abstract

Substituted tetrahydro-naphthalenes and analogous compounds are prepared by reducing or condensing appropriate functional substituents in substituted tetrahydro-naphthalenes and analogous compounds by customary methods and converting functional groups in this manner into the desired groups. The compounds according to the invention are suitable for use as active compounds in pharmaceuticals, in particular in pharmaceuticals for treating arteriosclerosis and also dyslipidaemias.

Compounds of the general formula (I),

in which
A represents cycloalkyl having 3 to 8 carbon atoms, or represents aryl having 6 to 10 carbon atoms, or
represents a 5- to 7-membered saturated, partially unsaturated or unsaturated, optionally benzo-fused heterocycle having up to 4 heteroatoms selected from the group consisting of S, N and/or O,
where aryl and the abovementioned heterocyclic ring systems may optionally be substituted up to 5 times by identical or different substituents selected from the group consisting of cyano, halogen, nitro, carboxyl, hydroxyl, trifluoromethyl, trifluoromethoxy, or by straight-chain or branched alkyl, acyl, hydroxyalkyl, alkylthio, alkoxycarbonyl, oxyalkoxycarbonyl or alkoxy having in each case up to 7 carbon atoms, or by a group of the formula —NR3R4
in which
R3 and R4 are identical or different and each represents hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms,
D represents a radical of the formula
in which
R5, R6 and R9 independently of one another each represent cycloalkyl having 3 to 6 carbon atoms, or
aryl having 6 to 10 carbon atoms or a 5- to 7-membered, optionally benzo-fused, saturated or unsaturated, mono-, bi- or tricyclic heterocycle having up to 4 heteroatoms selected from the group consisting of S, N and/or O,
where the cycles are optionally, in the case of the nitrogen-containing rings also via the N-function, substituted up to 5 times by identical or different constituents selected from the group consisting of halogen, trifluoromethyl, nitro, hydroxyl, cyano, carboxyl, trifluoromethoxy, straight-chain or branched acyl, alkyl, alkylthio, alkylalkoxy, alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, by aryl or trifluoromethyl-substituted aryl having in each case 6 to 10 carbon atoms or by an optionally benzo-fused aromatic 5- to 7-membered heterocycle having up to 3 heteroatoms selected from the group consisting of S, N and/or O,
and/or by a group of the formula —OR10, —SR12, —SO2R12 or —NR13R14,
in which
R10, R11 and R12 independently of one another each represent aryl having 6 to 10 carbon atoms which for its part is substituted up to 2 times by identical or different substituents selected from the group consisting of phenyl, halogen or by straight-chain or branched alkyl having up to 6 carbon atoms,
R13 and R14 are identical or different and are as defined above for R3 and R4,
or
R5 and/or R6 represents/represent a radical of the formula
R7 represents hydrogen, halogen or methyl,
and
R8 represents hydrogen, halogen, azido, trifluoromethyl, hydroxyl, trifluoromethoxy, straight-chain or branched alkoxy or alkyl having in each case up to 6 carbon atoms or a radical of the formula —NR15R16,
in which
R15 and R16 are identical or different and are as defined above for R3 and R4,
or
R7 and R8 together form a radical of the formula ═O or ═NR17,
in which
R17 represents hydrogen or straight-chain or branched alkyl, alkoxy or acyl having in each case up to 6 carbon atoms,
L represents a straight-chain or branched alkylene or alkenylene chain, having in each case up to 8 carbon atoms, which is optionally substituted up to 2 times by hydroxyl,
T and X are identical or different and each represents a straight-chain or branched alkylene chain having up to 8 carbon atoms,
or
T or X represents a bond,
V represents an oxygen or sulphur atom or represents a —NR18 group,
in which
R18 represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms or phenyl,
E represents cycloalkyl having 3 to 8 carbon atoms, or represents straight-chain or branched alkyl having up to 8 carbon atoms which is optionally substituted by cycloalkyl having 3 to 8 carbon atoms or hydroxyl, or represents phenyl, which is optionally substituted by halogen or trifluoromethyl,
R1 and R2 together form a straight-chain or branched alkylene chain, having up to 7 carbon atoms, which has to be substituted by a carbonyl group and/or by a radical of the formula
in which
a and b are identical or different and each represents a number 1, 2 or 3,
R19 represents hydrogen, cycloalkyl having 3 to 7 carbon atoms, straight-chain or branched silylalkyl having up to 8 carbon atoms or straight-chain or branched alkyl having up to 8 carbon atoms which is optionally substituted by hydroxyl, straight-chain or branched alkoxy having up to 6 carbon atoms or by phenyl which for its part may be substituted by halogen, nitro, trifluoromethyl, trifluoromethoxy or by phenyl or tetrazole-substituted phenyl,
and alkyl is optionally substituted by a group of the formula —OR22,
in which
R22 represents straight-chain or branched acyl having up to 4 carbon atoms or benzyl,
or
R19 represents straight-chain or branched acyl having up to 20 carbon atoms or benzoyl which is optionally substituted by halogen, trifluoromethyl, nitro or trifluoromethoxy, or straight-chain or branched fluoracyl having up to 8 carbon atoms and 9 fluorine atoms,
R20 and R21 are identical or different and each represents hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms,
or
R20 and R21 together form a 3- to 6-membered carbocycle,
and the alkylene chain which is formed by R1 and R2 is optionally substituted up to 6 times, optionally also geminally, by identical or different substituents selected from the group consisting of trifluoromethyl, hydroxyl, nitrile, halogen, carboxyl, nitro, azido, cyano, cycloalkyl or cycloalkyloxy having in each case 3 to 7 carbon atoms, by straight-chain or branched alkoxycarbonyl, alkoxy or alkylthio having in each case up to 6 carbon atoms or by straight-chain or branched alkyl having up to 6 carbon atoms which for its part is substituted up to 2 times by identical or different substituents selected from the group consisting of hydroxyl, benzyloxy, trifluoromethyl, benzoyl, straight-chain or branched alkoxy, oxyacyl and carboxyl having in each case up to 4 carbon atoms and/or phenyl which for its part may be substituted by halogen, trifluoromethyl or trifluoromethoxy,
and/or the alkylene chain which is formed by R1 and R2 is optionally substituted, also geminally, up to 5 times by identical or different substituents selected from the group consisting of phenyl, benzoyl, thiophenyl and sulphonylbenzyl, which for their part are optionally substituted by halogen, trifluoromethyl, trifluoromethoxy or nitro,
and/or the alkylene chain formed by R1 and R2 is optionally substituted by a radical of the formula
in which
c represents a number 1, 2, 3 or 4,
d represents a number 0 or 1,
R23 and R24 are identical or different and each represents hydrogen, cycloalkyl having 3 to 6 carbon atoms, straight-chain or branched alkyl having up to 6 carbon atoms, benzyl or phenyl, which is optionally substituted up to 2 times by identical or different substituents selected from the group consisting of halogen, trifluoromethyl, cyano, phenyl and nitro,
and/or the alkylene chain formed by R1 and R2 is optionally substituted by a spiro-linked radical of the formula
in which
w represents either an oxygen or a sulphur atom,
Y and Y′ together form a 2- to 6-membered straight-chain or branched alkylene chain,
e represents a number 1, 2, 3, 4, 5, 6 or 7,
f represents a number 1 or 2,
R25, R26, R27, R28, R29, R30 and R31 are identical or different and each represents hydrogen, trifluoromethyl, phenyl, halogen or straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms,
or
R25 and R26 or R27 and R28, in each case together, form a straight-chain or branched alkyl chain having up to 6 carbon atoms,
or
R25 and R26 or R27 and R28, in each case together, form a radical of the formula
in which
W is as defined above,
g represents a number 1, 2, 3, 4, 5, 6 or 7,
R32 and R33 together form a 3- to 7-membered heterocycle which contains an oxygen or sulphur atom or a group of the formula SO, SO2 or —NR34,
in which
R34 represents hydrogen, phenyl, benzyl or straight-chain or branched alkyl having up to 4 carbon atoms,
and stereoisomers, stereoisomer mixtures and salts thereof.

68 more elements

Substituted tetrahydronaphthaline and analogous compounds

Life of this patent

Substituted tetrahydronaphthaline and analogous compounds

Life of this patent

Abstract

Claims12