Substituted dihydropyrazolones for treating cardiovascular and hematological diseases

A compound of the formula (I)

• in which
• R1 represents a heteroaryl group of the formula
• wherein
• * denotes the linkage point with the dihydropyrazolone ring,
• A in each individual occurrence denotes C—R4 or N, wherein at most two ring members A represent N at the same time,
• and
• E denotes O, S or N—R5,
• R2 represents a heteroaryl group of the formula
• wherein
• # denotes the linkage point with the dihydropyrazolone ring, G in each individual occurrence denotes C—R6 or N, wherein at most two ring members G represent N at the same time,
• J denotes O, S or N—R7
• and
• L in each individual occurrence denotes C—R8 or N, wherein at most two ring members L represent N at the same time,
• wherein
• R4, R6 and R8 are identical or different and in each individual case, independently of one another, represents hydrogen or a substituent chosen from the series consisting of halogen, cyano, nitro, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, 4- to 10-membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl, —C(═O)—R9, —C(═O)—OR10, —C(═O)—NR11R12, —O—C(═O)—R13, —O—C(═O)—NR14R15, —NR16—C(═O)—R17, —NR18—C(═O)—OR19, —NR29—C(═O)—NR21R22, —NR23—SO2—R24, —SO2—R25, —SO2—NR26R27, —OR28, —SR29 and —NR39R31, wherein
• (i) (C1-C6)-alkyl in its turn can be substituted once to three times in an identical or different manner by radicals chosen from the series consisting of halogen, cyano, oxo, (C3-C7)-cycloalkyl, 4- to 10-membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl, —C(═O)—R9, —C(═O)—OR10, —C(═O)—NR11R12, —O—C(═O)—R13, —O—C(═O)—NR14R15, —NR16—C(═O)—R17, —NR18—C(═O)—OR19, —NR20—C(═O)—NR21R22, —NR23—SO2—R24, —SO2—R25, —SO2—NR26R27, —OR28, —SR29 and —NR39R31,
• wherein the cycloalkyl, heterocycloalkyl, phenyl and heteroaryl radicals mentioned last in their turn can in each case be substituted up to three times in an identical or different manner by halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and/or (C1-C4)-alkoxy-carbonyl,
• (ii) (C3-C7)-cycloalkyl, 4- to 10-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl in their turn can in each case be substituted once to three times in an identical or different manner by radicals chosen from the series consisting of (C1-C6)-alkyl, halogen, cyano, oxo, —C(═O)—R9, —C(═O)—OR10, —C(═O)—NR11R12, —O—C(═O)—R13, —O—C(═O)—NR14R15, —NR16—C(═O)—R17, —NR18—C(═O)—OR19, —NR20—C(═O)—NR21R22, —NR23—SO2—R24, —SO2—R25, —SO2—NR26R27, —OR28, —SR29 and —NR30R31,
• wherein the alkyl radical mentioned last can in its turn be substituted up to three times in an identical or different manner by halogen, cyano, hydroxyl, trifluoromethoxy, (C1-C4)-alkoxy, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and/or 5- or 6-membered heteroaryl,
• (iii) R9, R10, R11, R13, R14, R17, R19, R21, R24, R25, R26, R28, R29 and R30 independently of one another for each individual occurrence represent a radical chosen from the series consisting of hydrogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, 4- to 10-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl, wherein
• (C3-C7)-cycloalkyl, 4- to 10-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl in their turn can in each case be substituted up to three times in an identical or different manner by halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and/or (C1-C4)-alkoxycarbonyl
• and
• (C1-C6)-alkyl can be substituted once to three times in an identical or different manner by halogen, cyano, hydroxyl, trifluoromethoxy, (C1-C4)-alkoxy, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, (C3-C7)-cyclo alkyl, 4- to 7-membered heterocycloalkyl, phenyl and/or 5- or 6-membered heteroaryl,
• (iv) R12, R15, R16, R18, R20, R22, R23, R27 and R31 independently of one another for each individual occurrence represent a radical chosen from the series consisting of hydrogen and (C1-C6)-alkyl,
• wherein (C1-C6)-alkyl can be substituted once to three times in an identical or different manner by halogen, cyano, hydroxyl, trifluoromethoxy, (C1-C4)-alkoxy, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and/or (C1-C4)-alkoxycarbonyl,
• and/or wherein
• (v) R11 and R12, R14 and R15, R16 and R17, R18 and R19, R20 and R21, R21 and R22, R23 and R24, R26 and R27 and R30 and R31 in each case paired together with the atoms to which they are bonded can form a 5- or 6-membered heterocycloalkyl ring, which can be substituted once to three times in an identical or different manner by halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and/or (C1-C4)-alkoxycarbonyl,
• and
• R5 and R7 are identical or different and independently of one another represent hydrogen or a substituent chosen from the series consisting of (C1-C6)-alkyl, (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl, wherein
• (i) (C1-C6)-alkyl in its turn can be substituted once to three times in an identical or different manner by radicals chosen from the series consisting of halogen, cyano, oxo, (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl, —C(═O)—R9, —C(═O)—OR10, —C(═O)—NR11R12, —O—C(═O)—R13, —O—C(═O)—NR14R15, —NR16—C(═O)—R17, —NR18—C(═O)—OR19, —NR20—C(═O)—NR21R22, —NR23—SO2—R24, —SO2—R25, —SO2—NR26R27, —OR28, —SR29 and —NR30R31,
• wherein the cycloalkyl, heterocycloalkyl, phenyl and heteroaryl radicals mentioned last in their turn can in each case be substituted up to three times in an identical or different manner by halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and/or (C1-C4)-alkoxycarbonyl,
• and
• (ii) (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl in their turn can in each case be substituted once to three times in an identical or different manner by radicals chosen from the series consisting of (C1-C6)-alkyl, halogen, cyano, oxo, —C(═O)—R9, —C(═O)—OR10, —C(═O)—NR11R12, —O—C(═O)—R13, —O—C(═O)—NR14R15, —NR16—C(O)—R17, —NR18—C(O)—OR19, —NR20—C(═O)—NR21R22, —NR23—SO2—R24, —SO2—R25, —SO2—NR26R27, —OR28, —SR29 and —NR30R31,
• wherein the alkyl radical mentioned last in its turn can be substituted up to three times in an identical or different manner by halogen, cyano, hydroxyl, trifluoromethoxy, (C1-C4)-alkoxy, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and/or 5- or 6-membered heteroaryl,
• wherein
• (a) R9, R10, R11, R13, R14, R17, R19, R21, R24, R25, R26, R28, R29 and R30 independently of one another for each individual occurrence represent a radical chosen from the series consisting of hydrogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl, wherein
• (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl in their turn can in each case be substituted up to three times in an identical or different manner by halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and/or (C1-C4)-alkoxycarbonyl
• and
• (C1-C6)-alkyl can be substituted once to three times in an identical or different manner by halogen, cyano, hydroxyl, trifluoromethoxy, (C1-C4)-alkoxy, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, (C3-C7)-cyclo alkyl, 4- to 7-membered heterocycloalkyl, phenyl and/or 5- or 6-membered heteroaryl,
• (b) R12, R15, R16, R18, R20, R22, R23, R27 and R31 independently of one another for each individual occurrence represent a radical chosen from the series consisting of hydrogen and (C1-C6)-alkyl,
• wherein (C1-C6)-alkyl can be substituted once to three times in an identical or different manner by halogen, cyano, hydroxyl, trifluoromethoxy, (C1-C4)-alkoxy, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and/or (C1-C4)-alkoxycarbonyl,
• and/or
• (c) R11 and R12, R14 and R15, R16 and R17, R18 and R19, R20 and R21, R21 and R22, R23 and R24, R26 and R27 and R30 and R31 in each case paired together with the atoms to which they are bonded can form a 5- or 6-membered heterocycloalkyl ring, which can be substituted once to three times in an identical or different manner by halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and/or (C1-C4)-alkoxycarbonyl,
• and
• R3 represents hydrogen, (C1-C6)-alkyl or (C3-C7)-cyclo alkyl,
• and their salts, solvates and solvates of the salts,
• with the exception of the compounds
• 1H-pyrazol-5-yl)-2H-3-pyrazolin-5(1H)-one,
• 3′,5-dimethyl-2-phenyl-1′-(4-phenyl-1,3-thiazol-2-yl)-1′H,2H-3,4′-bipyrazol-5′-ol,
• 3′,5-dimethyl-2-phenyl-1′-(4-thiophen-2-yl-1,3-thiazol-2-yl)-1′H,2H-3,4′-bipyrazol-5′-ol,
• 3′,5-dimethyl-1′-(4-methyl-1,3-thiazol-2-yl)-2-phenyl-1′H,2H-3,4′-bipyrazol-5′-ol,
• 2-(4-chlorophenyl)-3′,5-dimethyl-1′-(4-phenyl-1,3-thiazol-2-yl)-1′H,2H-3,4′-bipyrazol-5′-ol and
• 2-ten-butyl-1′-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-3′,5-dimethyl-1′H,2H-3,4′-bipyrazol-5′-ol.