Substituted dihydropyrazolones and use thereof as HIF-prolyl-4-hydroxylase inhibitors

A compound of the formula (I)

• in which
• R1 represents a heteroaryl group of the formula
• where
• * represents the point of attachment to the dihydropyrazolone ring,
• A in each individual occurrence represents C—R4 or N, where at most two ring members A represent N at the same time,
• and
• E in each individual occurrence represents C—R5 or N, where at most two ring members E represent N at the same time,
• R2 represents a heteroaryl group of the formula
• where
• # represents the point of attachment to the dihydropyrazolone ring,
• G in each individual occurrence represents C—R6 or N,
• J represents O, S or N—R7,
• L in each individual occurrence represents C—R8 or N, where at most two ring members L represent N at the same time,
• and
• M in each individual occurrence represents C—R9 or N, where in total one or two ring members M represent N,
• where
• R4, R6, R8 and R9 are identical or different and in each individual case independently of one another represent hydrogen or a substituent selected from the group consisting of halogen, cyano, nitro, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, 4- to 10-membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl, —C(═O)—R10, —C(═O)—OR11, —C(═O)—NR12R13, —O—C(═O)—R14, —O—C(═O)—NR15R16, —NR17—C(═O)—R18, —NR19—C(═O)—OR20, —NR21—C(═O)—NR22R23, —NR24—SO2—R25, —SO2—R26, —SO2—NR27R28, —OR29, —SR30 and —NR31R32, where
• (i) (C1-C6)-alkyl for its part may be mono- to trisubstituted by identical or different radicals selected from the group consisting of halogen, cyano, oxo, (C3-C7)-cycloalkyl, 4- to 10-membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl, —C(═O)—R10, —C(═O)—OR11, —C(═O)—NR12R13, —O—C(═O)—R14, —O—C(═O)—NR15R16, —NR17—C(═O)—R18, —NR19—C(═O)—OR20, —NR21—C(═O)—NR22R23, —NR24—SO2—R25, —SO2—R26, —SO2—NR27R28, —OR29, —SR30 and —NR31R32,
• where the last-mentioned cycloalkyl, heterocycloalkyl, phenyl and heteroaryl radicals for their part may in each case be substituted up to three times by identical or different substituents from the group consisting of halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and (C1-C4)-alkoxycarbonyl,
• (ii) (C3-C7)-cycloalkyl, 4- to 10-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl for their part may in each case be mono- to trisubstituted by identical or different radicals selected from the group consisting of (C1-C6)-alkyl, (C3-C7)-cycloalkyl, halogen, cyano, oxo, —C(═O)—R10, —C(═O)—OR11, —C(═O)—NR12R13, —O—C(═O)—R14, —O—C(═O)—NR15R16, —NR17—C(═O)—R18, —NR19—C(═O)—OR20, —NR21—C(═O)—NR22R23, —NR24—SO2—R25, —SO2—R26, —SO2—NR27R28, —OR29, —SR30 and —NR31R32,
• where the last-mentioned alkyl radical for its part may be substituted up to three times by identical or different substituents from the group consisting of 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 5- or 6-membered heteroaryl,
• (iii) R10, R11, R12, R14, R15, R18, R20, R22, R25, R26, R27, R29, R30 and R31 independently of one another in each individual occurrence represent a radical selected from the group consisting of hydrogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl, where
• (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl for their part may in each case be substituted up to three times by identical or different substituents from the group consisting of halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and (C1-C4)-alkoxycarbonyl
• and
• (C1-C6)-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of 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 5- or 6-membered heteroaryl,
• where the last-mentioned heterocycloalkyl radical for its part may be substituted up to two times by identical or different substituents from the group consisting of (C1-C4)-alkyl,
• (iv) R13, R16, R17, R19, R21, R23, R24, R28 and R32 independently of one another in each individual occurrence represent a radical selected from the group consisting of hydrogen and (C1-C6)-alkyl,
• where (C1-C6)-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, trifluoromethoxy, (C1-C4)-alkoxy, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and (C1-C4)-alkoxycarbonyl,
• and/or where
• (v) R12 and R13, R15 and R16, R17 and R18, R19 and R20, R21 and R22, R22 and R23, R24 and R25, R27 and R28 and also R31 and R32 in each case as a pair together with the atoms to which they are attached may form a 5- or 6-membered heterocycloalkyl ring which may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and (C1-C4)-alkoxycarbonyl,
• R5 in each individual case, independently of one another, represents hydrogen or a substituent selected from the group consisting of halogen, cyano, nitro, (C1-C6)-alkyl, trifluoromethyl, hydroxyl, (C1-C6)-alkoxy, trifluoromethoxy, amino, mono-(C1-C6)-alkylamino, di-(C1-C6)-alkylamino, hydroxycarbonyl and (C1-C6)-alkoxycarbonyl
• and
• R7 represents hydrogen or a substituent selected from the group consisting of (C1-C6)-alkyl, (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl, where
• (i) (C1-C6)-alkyl for its part may be mono- to trisubstituted by identical or different radicals selected from the group consisting of halogen, cyano, oxo, (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl, —C(═O)—R10, —C(═O)—OR11, —C(═O)—NR12R13, —O—C(═O)—R14, —O—C(═O)—NR15R16, —NR17—C(═O)—R18, —NR19—C(═O)—OR20, —NR21—C(═O)—NR22R23, —NR24—SO2—R25, —SO2—R26, —SO2—NR27R28, —OR29, —SR30 and —NR31R32,
• where the last-mentioned cycloalkyl, heterocycloalkyl, phenyl and heteroaryl radicals for their part may in each case be substituted up to three times by identical or different substituents from the group consisting of halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and (C1-C4)-alkoxycarbonyl,
• and
• (ii) (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl for their part may in each case be mono- to trisubstituted by identical or different radicals selected from the group consisting of (C1-C6)-alkyl, halogen, cyano, oxo, —C(═O)—R10, —C(═O)—OR11, —C(═O)—NR12R13, —O—C(═O)—R14, —O—C(═O)—NR15R16, —NR17—C(═O)—R18, —NR19—C(═O)—OR20, —NR21—C(═O)—NR22R23, —NR24—SO2—R25, —SO2—R26, —SO2—NR27R28, —OR29, —SR30 and —NR31R32,
• where the last-mentioned alkyl radical for its part may be substituted up to three times by identical or different substituents from the group consisting of 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 5- or 6-membered heteroaryl,
• where
• (a) R10, R11, R12, R14, R15, R18, R20, R22, R25, R26, R27, R29, R30 and R31 independently of one another in each individual occurrence represent a radical selected from the group consisting of hydrogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl, where
• (C3-C7)-cycloalkyl, 4- to 7-membered heterocycloalkyl, phenyl and 5- or 6-membered heteroaryl for their part may in each case be substituted up to three times by identical or different substituents from the group consisting of halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and (C1-C4)-alkoxycarbonyl
• and
• (C1-C6)-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of 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 5- or 6-membered heteroaryl,
• (b) R13, R16, R17, R19, R21, R23, R24, R28 and R32 independently of one another in each individual occurrence represent a radical selected from the group consisting of hydrogen and (C1-C6)-alkyl,
• where (C1-C6)-alkyl may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, trifluoromethoxy, (C1-C4)-alkoxy, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and (C1-C4)-alkoxycarbonyl,
• and/or
• (c) R12 and R13, R15 and R16, R17 and R18, R19 and R20, R21 and R22, R22 and R23, R24 and R25, R27 and R28 and also R31 and R32 in each case as a pair together with the atoms to which they are attached may form a 5- or 6-membered heterocycloalkyl ring which may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, (C1-C4)-alkyl, trifluoromethyl, hydroxyl, (C1-C4)-alkoxy, trifluoromethoxy, oxo, amino, mono-(C1-C4)-alkylamino, di-(C1-C4)-alkylamino, hydroxycarbonyl and (C1-C4)-alkoxycarbonyl,
• and
• R3 represents hydrogen, (C1-C6)-alkyl or (C3-C7)-cycloalkyl,
• and salts, solvates and solvates of the salts thereof.