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US 6,833,364 B1Granted
Substituted pyrazole derivatives
AssigneeBayer HealthCare LLC
InventorsAlexander Straub, Achim Feurer, Cristina Alonso-Alija, Elke Stahl, Johannes-Peter Stasch, Elisabeth Perzborn, Joachim Hütter, Klaus Dembowsky
Life of this patent
Estimating the term…
Abstract
The present invention relates to novel substituted pyrazole derivatives of the general formula (I) in which the substituents R1, R2, R3, A, X and Y are each as defined, and to processes for their preparation and to their use as medicaments, in particular as medicaments for the treatment of cardiovascular disorders.
Claims13
A compound of the formula (I)
- in which
- at least one of the substituents R1, X and Y represents saturated or partially unsaturated C3-C8-cycloalkyl,
- which may optionally be mono- or polysubstituted by amino, azido, formyl, mercaptyl, carboxyl, hydroxyl, morpholino, piperidino, pyrrolidino, sulphonamino, straight-chain, cyclic or branched acyl, acylamino, alkoxy, benzyloxy, alkylamino, dialkylamino, alkylsulphonyl, alkylsulphonamino, alkylthio, alkoxycarbonyl having in each case up to 6 carbon atoms, nitro, cyano, halogen, phenyl and/or is optionally substituted by
- straight-chain or branched or cyclic alkyl having up to 6 carbon atoms which for its part may be substituted by amino, mercaptyl, carboxyl, hydroxyl, morpholino, piperidino, pyrrolidino, straight-chain, cyclic or branched acyl, acylamino, alkoxy, alkylamino, dialkylamino, alkylsulphonyl, alkylthio, phenyl, alkylsulphonamino, alkoxycarbonyl having in each case up to 6 carbon atoms, nitro, cyano, halogen,
- and where the optionally remaining radicals R1, X and/or Y are identical or different and each represents hydrogen, azido, formyl, mercaptyl, carboxyl, hydroxyl, straight-chain or branched acyl, alkoxy, alkylthio or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro, cyano, halogen, phenyl or straight-chain or branched alkenyl or alkinyl having in each case up to 6 carbon atoms or alkyl having up to 20 carbon atoms, where both alkenyl, alkinyl and/or alkyl may optionally be substituted by hydroxyl, amino, azido, carboxyl, straight-chain or branched acyl, alkoxy, alkoxycarbonyl or acylamino having in each case up to 5 carbon atoms, aryl having 6 to 10 carbon atoms, halogen, cyano, dialkylamino having up to 6 carbon atoms, alkylamino having up to 6 carbon atoms and/or cycloalkyl having 3 to 8 carbon atoms or by a radical of the formula —OR4,
- in which
- R4 represents straight-chain or branched acyl having up to 5 carbon atoms,
- and/or the optionally remaining radicals R1, X and/or Y each represents a radical of the formula
- in which
- a, b and b′ are identical or different and represent a number 0, 1, 2 or 3,
- R5 represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms,
- and/or the optionally remaining radicals R1, X and/or Y each represent a 1,3-oxazolidin-2-on-3-yl group which is optionally mono- or polysubstituted by identical or different substituents from the group consisting of straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl, amino, halogen, carboxyl, straight-chain or branched acyl, alkoxy, alkoxycarbonyl or acylamino having in each case up to 5 carbon atoms,
- and/or the optionally remaining radicals R1, X and/or Y each represent straight-chain or branched acyl having up to 6 carbon atoms which is optionally substituted by halogen, or
- represent straight-chain or branched acyloxy having up to 6 carbon atoms, or
- represent arylthio having 6 to 10 carbon atoms,
- and/or the optionally remaining radicals R1, X and/or Y represent radicals of the formulae —SO3H or S(O)2R6,
- in which
- c represents a number 1 or 2,
- R6 represents straight-chain or branched alkyl having 1 to 10 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, or aryl having 6 to 10 carbon atoms where the ring systems may optionally be substituted by halogen or by straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms,
- and/or the optionally remaining radicals R1, X and/or Y each represent a radical of the formula PO(OR7)(OR8),
- in which
- R7 and R8 are identical or different and each represents hydrogen, straight-chain or branched alkyl having up to 8 carbon atoms or cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or benzyl,
- and/or the optionally remaining radicals R1, X and/or Y each represent oxycycloalkyl having 3 to 8 carbon atoms or represent radicals of the formulae —NH—C(═NH)NH2, CON═C(NH2)2 or —C═NH(NH2), (CO)dNR9R10 or —NHCONR9′R10′,
- in which
- d represents a number 0 or 1,
- R9 and R10 are identical or different and each represents hydrogen, straight-chain or branched alkyl having up to 14 carbon atoms or cycloalkyl having 3 to 14 carbon atoms, or aryl having 6 to 10 carbon atoms, where the abovementioned radicals may optionally be substituted by aryl having 6 to 10 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, hydroxyl, amino or straight-chain or branched alkoxy, acyl or alkoxycarbonyl having in each case up to 6 carbon atoms,
- and in the case that d=0,
- R9 and R10 may also represent straight-chain, branched or cyclic acyl having up to 14 carbon atoms, straight-chain or branched hydroxyalkyl having up to 6 carbon atoms, straight-chain or branched alkoxyalkyl having a total of up to 12 carbon atoms, straight-chain or branched alkoxycarbonyl or acyloxyalkyl having in each case up to 6 carbon atoms or a radical of the formula —SO2R11 or radicals of the formulae
- in which
- R11 represents straight-chain or branched alkyl having up to 4 carbon atoms, and/or
- R9 and R10 represents radicals of the formulae
- in which
- R12, R13 and R15 to R18 and R23 to R28 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms,
- e represents a number 0, 1 or 2, and
- R14 represents straight-chain or branched alkyl having up to 6 carbon atoms or cycloalkyl having 3 to 8 carbon atoms,
- R9′ and R10′ are identical or different and each represents hydrogen;
- alkyl having up to 14 carbon atoms which is optionally substituted by hydroxyl or alkoxy having up to 8 carbon atoms;
- aryl having 6 to 10 carbon atoms which is optionally substituted by halogen,
- R2 and R3 form, together with the double bond, a fused phenyl ring or a fused 6-membered aromatic heterocycle having up to 2 N atoms as the heteroatom(s),
- which is optionally substituted up to 3 times by identical or different substituents from the group consisting of formyl, carboxyl, hydroxyl, mercaptyl, straight-chain or branched acyl, alkylthio or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro, cyano, halogen or straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms which for its part may be substituted by hydroxyl, amino, carboxyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 5 carbon atoms,
- and/or the fused phenyl ring or the fused 6-membered aromatic heterocycle is optionally substituted by a group of the formula —NR29R30,
- in which
- R29 and R30 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms, or
- R29 represents hydrogen and
- R30 represents acyl having up to four carbon atoms
- and/or the fused phenyl ring or fused 6-membered aromatic heterocycle are optionally substituted by phenyl which for its part may be substituted up to 2 times by identical or different substituents from the group consisting of halogen, straight-chain or branched alkyl and alkoxy having in each case up to 6 carbon atoms
- and/or the fused phenyl ring or the fused 6-membered aromatic heterocycle are optionally substituted by a group of the formula —N═CH—NR31R32,
- in which
- R31 and R32 are identical or different and each represents hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms,
- A represents phenyl or pyrimidyl group,
- which is optionally substituted up to 3 times by identical or different substituents from the group consisting of amino, mercaptyl, hydroxyl, formyl, carboxyl, straight-chain or branched acyl, alkylthio, alkyloxyacyl, alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro, cyano, trifluoromethyl, azido, halogen, phenyl and straight-chain or branched alkyl having up to 6 carbon atoms which for its part may be substituted by hydroxyl, carboxyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 5 carbon atoms, and/or
- is substituted by a group of the formula —(CO)f—NR33R34,
- in which
- f represents a number 0 or 1,
- R33 and R34 are identical or different and represent hydrogen, phenyl, benzyl or straight-chain or branched alkyl or acyl having in each case up to 5 carbon atoms,
- or a pharmaceutically acceptable isomeric form or salt thereof.
53 more elements
Dependencies are inferred from the claim text.