US 6,207,671 B1 · Cycloalkano-pyridines

Abstract

The cycloalkano-pyridines are prepared by reacting corresponding cycloalkano-pyridine-aldehydes with suitable organometallic compounds or Wittig or Grignard reagents or reacting compounds of the cycloalkano-pyridine alcohols type with suitable bromine compounds, and optionally varying the functional groups accordingly. The cycloalkanopyridines are suitable as active compounds in medicaments, in particular in medicaments for the treatment of hypertipoproteinaemia and arteriosclerosis.

Cycloalkano-pyridines of the general formula (I)

in which
A represents aryl having 6 to 10 carbon atoms, which is optionally substituted up to 5 times in an identical or different manner by halogen, nitro, hydroxyl, trifluoromethyl, trifluoromethoxy, or by straight-chain or branched alkyl, acyl, hydroxyalkyl or alkoxy each having up to 7 carbon atoms, or by a group of the formula —NR3R4,
in which
R3 and R4 are identical or different and denote hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms,
D represents aryl having 6 to 10 carbon atoms, which is optionally substituted by phenyl, nitro, halogen, trifluoromethyl or trifluoromethoxy, or represents a radical of the formula
in which
R5 and R6 and R9 independently of one another denote cycloalkyl having 3 to 6 carbon atoms, or denote 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 from the series S, N and/or O, where the cycles are substituted, if appropriate, in the case of the nitrogen-containing rings also via the N function, up to 5 times in an identical or different manner by halogen, trifluoromethyl, nitro, hydroxyl, cyano, carboxyl, trifluoromethoxy, straight-chain or branched acyl, alkyl, alkylthio, alkylalkoxy, alkoxy or alkoxycarbonyl each having up to 6 carbon atoms, by aryl- or trifluoromethyl-substituted aryl each having 6 to 10 carbon atoms or by an optionally benzo-fused, aromatic 5- to 7-membered heterocycle having up to 3 heteroatoms from the series S, N and/or O, and/or are substituted by a group of the formula —OR10, —SR11, —SO2R12 or —NR13R14,
in which
R10, R11 and R12 independently of one another denote aryl having 6 to 10 carbon atoms, which for its part is substituted up to 2 times in an identical or different manner by phenyl, halogen or by straight-chain or branched alkyl having up to 6 carbon atoms,
R13 and R14 are identical or different and have the meaning of R3 and R4 indicated above,
or
R5 and/or R6 denote a radical of the formula
R7 denotes hydrogen or halogen
and
R8 denotes hydrogen, halogen, azido, trifluoromethyl, hydroxyl, trifluoromethoxy, straight-chain or branched alkoxy or alkyl each having up to 6 carbon atoms or a radical of the formula —NR15R16,
in which
R15 and R16 are identical or different and have the meaning of R3 and R4 indicated above,
or
R7 and R8 together form a radical of the formula ═O or ═NR17,
in which
R17 denotes hydrogen or straight-chain or branched alkyl, alkoxy or acyl each having up to 6 carbon atoms,
L denotes a straight-chain or branched alkylene or alkenylene chain each having up to 8 carbon atoms, each of which is optionally substituted up to 2 times by hydroxyl,
T and X are identical or different and denote a straight-chain or branched alkylene chain having up to 8 carbon atoms,
or
T or X denotes a bond,
V represents an oxygen or sulphur atom or an —NR18 group,
in which
R18 denotes 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 must be substituted by a carbonyl group and/or by a radical of the formula
in which
a and b are identical or different and denote a number 1, 2 or 3,
R19 denotes 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 can 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 denotes straight-chain or branched acyl having up to 4 carbon atoms or benzyl,
or
R19 denotes straight-chain or branched acyl having up to 20 carbon atoms or benzoyl which is optionally substituted by halogen, trifluoromethyl, nitro or trifluoromethoxy, or
denotes straight-chain or branched fluoroacyl having up to 8 carbon atoms and 9 fluorine atoms,
R20 and R21 are identical or different, and denote 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, if appropriate also geminally, the carbocycles formed are optionally substituted up to 6 times in an identical or different manner by trifluoromethyl, hydroxyl, halogen, carboxyl, nitro, azido, cyano, cycloalkyl or cycloalkyloxy each having 3 to 7 carbon atoms, by straight-chain or branched alkoxycarbonyl, alkoxy or alkylthio each having 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 in an identical or different manner by hydroxyl, benzyloxy, trifluoromethyl, benzoyl, straight-chain or branched alkoxy, oxyacyl or carboxyl each having up to 4 carbon atoms and/or phenyl, which for its part can be substituted by halogen, trifluoromethyl or trifluoromethoxy,
and/or the carbocycles formed, also geminally, are optionally substituted up to 5 times in an identical or different manner by phenyl, benzoyl, thiophenyl or sulphonylbenzyl, which for their part are optionally substituted by halogen, trifluoromethyl, trifluoromethoxy or nitro,
and/or are optionally substituted by a radical of the formula
in which
c denotes a number 1, 2, 3 or 4,
d denotes a number 0 or 1,
R23 and R24 are identical or different and denote 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 in an identical or different manner by halogen, trifluoromethyl, cyano, phenyl or nitro,
and/or the carbocycles formed are optionally substituted by a spiro-linked radical of the formula
in which
W either denotes an oxygen or a sulphur atom,
Y and Y′ together form a 2- to 6-membered straight-chain or branched alkylene chain,
e denotes a number 1, 2, 3, 4, 5, 6 or 7,
f denotes a number 1 or 2,
R25, R26, R27, R28, R29, R30 and R31 are identical or different and denote hydrogen, trifluoromethyl, phenyl, halogen or straight-chain or branched alkyl or alkoxy each having 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 has the meaning indicated above,
g denotes 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 denotes hydrogen, phenyl, benzyl or straight-chain or branched alkyl having up to 4 carbon atoms,
and their salts and N-oxides, with the exception of 5(6H)-quinolone, 3-benzoyl-7,8-dihydro-2,7,7-trimethyl-4-phenyl.

64 more elements

Cycloalkano-pyridines

Life of this patent

Cycloalkano-pyridines

Life of this patent

Abstract

Claims8