CA2309332C - 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors - Google Patents

2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors Download PDF

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CA2309332C
CA2309332C CA002309332A CA2309332A CA2309332C CA 2309332 C CA2309332 C CA 2309332C CA 002309332 A CA002309332 A CA 002309332A CA 2309332 A CA2309332 A CA 2309332A CA 2309332 C CA2309332 C CA 2309332C
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CA2309332A1 (en
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Ulrich Niewohner
Mazen Es-Sayed
Helmut Haning
Thomas Schenke
Karl-Heinz Schlemmer
Jorg Keldenich
Erwin Bischoff
Elisabeth Perzborn
Klaus Dembowsky
Peter Serno
Marc Nowakowski
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Bayer Intellectual Property GmbH
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Bayer AG
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Priority to DE1997150085 priority Critical patent/DE19750085A1/en
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Priority to DE19812462.7 priority
Priority to DE1998112462 priority patent/DE19812462A1/en
Priority to DE19840289.9 priority
Priority to DE1998140289 priority patent/DE19840289A1/en
Priority to PCT/EP1998/006910 priority patent/WO1999024433A1/en
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

Abstract

The 2-phenyl-substituted imidazotriazinones having short, unbranched alkyl radicals in the 9-position are prepared from the corresponding 2-phenyl-imidazotriazinones by chlorosulphonation and subsequent reaction with the amines. The compounds inhibit cGMP-metabolizing phosphodiesterases and are suitable for use as active compounds in pharmaceuticals, for the treatment of cardiovascular and cerebrovascular disorders and/or disorders of the urogenital system, in particular for the treatment of erectile dysfunction.

Claims (30)

1. 2-Phenyl-substituted imidazotriazinones of the general formula (I) in which R1 represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, R2 represents straight-chain alkyl having up to 4 carbon atoms, R3 and R4 are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to 8 carbon atoms, or represents a straight-chain or branched alkyl chain having up to 10 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of trifluoromethyl, trifluoromethoxy, hydroxyl, halogen, carboxyl, benzyloxycarbonyl, straight-chain or branched alkoxycarbonyl having up to 6 carbon atoms and/or by radicals of the formulae -SO3H, -(A)a-NR7R8, -O-CO-NR7R8, -S(O)b-R9, -P(O)(OR10)(OR11), in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or SO2, R7, R7', R8 and R8' are identical or different and each represents hydrogen, or represents cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms, a 5- to 6-membered unsaturated, partially unsaturated or saturated, optionally benzo-fused heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, where the abovementioned ring systems are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, nitro, trifluoromethyl, trifluoromethoxy, carboxyl, halogen, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms or by a group of the formula -(SO2)c-NR12R13, in which c represents a number 0 or 1, R12 and R13 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms, or R7, R7', R8 and R8' each represent straight-chain or branched alkoxy having up to 6 carbon atoms, or represents straight-chain or branched alkyl having up to 8 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, halogen, aryl having 6 to 10 carbon atoms, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms or by a group of the formula -(CO)d-NR14R15, in which R14 and R15 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and d represents a number 0 or 1, or R7 and R8 and/or R7' and R8' together with the nitrogen atom form a 5- to 7-membered saturated heterocycle which may optionally contain a further heteroatom from the group consisting of S and O or a radical of the formula -NR16, in which R16 represents hydrogen, aryl having 6 to 10 carbon atoms, benzyl, a 5- to 7-membered aromatic or saturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and O
which is optionally substituted by methyl, or represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl, R9 represents aryl having 6 to 10 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms, R10 and R11 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and/or the alkyl chain listed above under R3/R4 is optionally substituted by cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or by a 5- to 7-membered partially unsaturated, saturated or unsaturated, optionally benzo-fused heterocycle which may contain up to 4 heteroatoms from the group consisting of S, N
and O or a radical of the formula -NR17, in which R17 represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl or alkoxy having in each case up to 4 carbon atoms, or represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl and straight-chain or branched alkoxy having up to 6 carbon atoms, and where aryl and the heterocycle are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of nitro, halogen, -SO3H, straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy and/or by a radical of the formula -SO2-NR18R19, in which R18 and R19 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms, and/or R3 or R4 represents a group of the formula -NR20R21, in which R20 and R21 have the meanings of R18 and R19 given above and are identical to or different from them, and/or R3 or R4 represents adamantyl, or represents radicals of the formulae or represents cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or represents a 5- to 7-membered partially unsaturated, saturated or unsaturated, optionally benzo-fused heterocycle which may contain up to 4 heteroatoms from the group consisting of S, N and O, or a radical of the formula -NR22, in which R22 has the meaning of R16 given above and is identical to or different from it, or represents carboxyl, formyl or straight-chain or branched acyl having up to 5 carbon atoms, and where cycloalkyl, aryl and/or the heterocycle are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, triazolyl, trifluoromethyl, trifluoromethoxy, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro and/or by groups of the formulae -SO3H, -OR23, (SO2)e NR24R25, -P(O)(OR26)(OR27), in which e represents a number 0 or 1, R23 represents a radical of the formula represents cycloalkyl having 3 to 7 carbon atoms, or represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms which is optionally substituted by cycloalkyl having 3 to 7 carbon atoms, benzyloxy, tetrahydropyranyl, tetrahydrofuranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, carboxyl, benzyloxycarbonyl or phenyl which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkoxy having up to 4 carbon atoms, hydroxyl and halogen, and/or alkyl which is optionally substituted by radicals of the formulae -CO-NR28R29 or -CO-R30, in which R28 and R29 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 8 carbon atoms, or R28 and R29 together with the nitrogen atom form a 5- to 7-membered saturated heterocycle which may optionally contain a further heteroatom from the group consisting of S and O, and R30 represents phenyl or adamantyl, R24 and R25 have the meanings of R18 and R19 given above and are identical to or different from them, R26 and R27 have the meanings of R10 and R11 given above and are identical to or different from them and/or cycloalkyl, aryl and/or the heterocycle are optionally substituted by straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl, carboxyl, by a 5- to 7-membered heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, or by groups of the formula -SO2-R31, P(O)(OR32)(OR33) or -NR34R35, in which R31 represents hydrogen or has the meaning of R9 given above and is identical to or different from it, R32 and R33 have the meanings of R10 and R11 given above and are identical to or different from them, R34 and R35 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl or by straight-chain or branched alkoxy having up to 4 carbon atoms, or R34 and R35 together with the nitrogen atom form a 5- to 6-membered saturated heterocycle which may contain a further heteroatom from the group consisting of S and O, or a radical of the formula -NR36, in which R36 represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 7 carbon atoms or straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl, or R3 and R4 together with the nitrogen atom form a 5- to 7-membered unsaturated or saturated or partially unsaturated, optionally benzo-fused heterocycle which may optionally contain up to 3 heteroatoms from the group consisting of S, N and O, or a radical of the formula -NR37, in which R37 represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, trifluoromethyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, or by groups of the formula -(D)f -NR38R39, -CO-(CH2)g -O-CO-R40, -CO-(CH2)h-OR41 or -P(O)(OR42)(OR43), in which g and h are identical or different and each represents a number l, 2, 3 or 4, and f represents a number 0 or 1, D represents a group of the formula -CO or -SO2, R38 and R39 are identical or different and each has the meaning of R7 and R8 given above, R40 represents straight-chain or branched alkyl having up to 6 carbon atoms, R41 represents straight-chain or branched alkyl having up to 6 carbon atoms, R42 and R43 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or R37 represents a radical of the formula -(CO)i -E, in which i represents a number 0 or 1, E represents cycloalkyl having 3 to 7 carbon atoms or benzyl, represents aryl having 6 to 10 carbon atoms or a 5- to 6-membered aromatic heterocycle having up to 4 heteroatoms from the group consisting of S, N and O, where the abovementioned ring systems are optionally mono- or polysubstituted by identical or different constituents selected from the group consisting of nitro, halogen, -SO3H, straight-chain or branched alkoxy having up to 6 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy, or by a radical of the formula -SO2-NR44R45, in which R44 and R45 have the meaning of R18 and R19 given above and are identical to or different from them, or E represents radicals of the formulae and the heterocycle listed under R3 and R4, which is formed together with the nitrogen atom, is optionally mono- or polysubstituted, if appropriate also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro and groups of the formulae -P(O)(OR46)(OR47), = NR48 or ~ (CO)j NR49R50 in which R46 and R47 have the meanings of R10 and R11 given above and are identical to or different from them, R48 represents hydroxyl or straight-chain or branched alkoxy having up to 4 carbon atoms, j represents a number 0 or 1, and R49 and R50 are identical or different and have the meanings of R14 and R15 given above, and/or the heterocycle listed under R3 and R4, which is formed together with the nitrogen atom, is optionally substituted by straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, halogen, carboxyl, cycloalkyl or cycloalkyloxy having in each case 3 to 8 carbon atoms, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, or by a radical of the formula -SO3H, -NR51R52 or P(O)OR53OR54, in which R51 and R52 are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, R53 and R54 are identical or different and have the meanings of R10 and R11 given above, and/or the alkyl is optionally substituted by aryl having 6 to 10 carbon atoms which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, hydroxyl, straight-chain or branched alkoxy having up to 6 carbon atoms, or by a group of the formula -NR51'R52', in which R51' and R52' have the meanings of R51 and R52 given above and are identical to or different from them, and/or the heterocycle listed under R3 and R4, which is formed together with the nitrogen atom, is optionally substituted by aryl having 6 to 10 carbon atoms or by a 5- to 7-membered saturated, partially unsaturated or unsaturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, optionally also attached via a nitrogen function, where the ring systems for their part may be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, or R3 and R4 together with the nitrogen atom form radicals of the formulae R5 and R6 are identical or different and each represents hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, hydroxyl or represents straight-chain or branched alkoxy having up to 6 carbon atoms, and their salts, hydrates, N-oxides and isomeric forms.
2-Phenyl-substituted imidazotriazinones of the general formula (I) according to Claim 1 in which R1 represents straight-chain or branched alkyl having up to 3 carbon atoms, R2 represents straight-chain alkyl having up to 3 carbon atoms, R3 and R4 are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to 6 carbon atoms, or represents a straight-chain or branched alkyl chain having up to 8 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, benzyloxycarbonyl, straight-chain or branched alkoxycarbonyl having up to 5 carbon atoms, and by radicals of the formulae -SO3H, -(A)a-NR7R8, -O-CO-NR7'R8', -S(O)b-R9, -P(O)(OR10)(OR11), in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or SO2, R7, R7', R8 and R8' are identical or different and each represents hydrogen, or cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, piperidinyl and pyridyl, where the abovementioned ring systems are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, nitro, trifluoromethyl, trifluoromethoxy, carboxyl, fluorine, chlorine, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a group of the formula -(SO2)c-NR12R13, in which c represents a number 0 or 1, R12 and R13 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or R7, R7', R8 and R8' each represent straight-chain or branched alkoxy having up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 7 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, phenyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a group of the formula -(CO)d-NR14R15, in which R14 and R15 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and d represents a number 0 or 1, or R7 and R8 and/or R7' and R8' together with the nitrogen atom form a pyrrolidinyl, morpholinyl, piperidinyl or triazolyl ring or radicals of the formulae in which R16 represents hydrogen, phenyl, benzyl, morpholinyl, pyrrolidinyl, piperidinyl, piperazinyl or N-methylpiperazinyl, or represents straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl, R9 represents straight-chain or branched alkyl having up to 3 carbon atoms, R10 and R11 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and/or the alkyl chain listed under R3/R4 is optionally substituted by cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, pyridyl, quinolyl, pyrrolidinyl, pyrimidyl, morpholinyl, furyl, piperidinyl, tetrahydrofuranyl or by radicals of the formulae in which R17 represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl or alkoxy having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl and straight-chain or branched alkoxy having up to 4 carbon atoms, and where phenyl and the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, -SO3H, straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms, hydroxyl, and/or by a radical of the formula -SO2NR18R19, in which R18 and R19 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and/or R3 or R4 represents a group of the formula -NR20R21, in which R20 and R21 have the meanings of R18 and R19 given above and are identical to or different from them, and/or R3 or R4 represents adamantyl, or represents radicals of the formulae or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl, morpholinyl, oxazolyl, thiazolyl, quinolyl, isoxazolyl, pyridyl, tetrahydrofuranyl, tetrahydropyranyl or represents radicals of the formulae in which R22 has the meaning of R16 given above and is identical to or different from it, or represents carboxyl, formyl or straight-chain or branched acyl having up to 3 carbon atoms, and where cycloalkyl, phenyl and/or the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, triazolyl, trifluoromethyl, trifluoromethoxy, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 5 carbon atoms, nitro and/or by groups of the formulae -SO3H, -OR23, (SO2)e NR24R25, -P(O)(OR26)(OR27), in which e represents a number 0 or 1, R23 represents a radical of the formula represents cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl or cycloheptyl, represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms which may optionally be substituted by cyclopropyl, cyclopentyl, cyclohexyl, benzyloxy, tetrahydropyranyl, tetrahydrofuranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, benzyloxycarbonyl or phenyl which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkoxy having up to 3 carbon atoms, hydroxyl, fluorine and chlorine, and/or where alkyl is optionally substituted by radicals of the formulae -CO-NR28R29 or -CO-R30, in which R28 and R29 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms, or R28 and R29 together with the nitrogen atom form a morpholinyl, pyrrolidinyl or piperidinyl ring, and R30 represents phenyl or adamantyl, R24 and R25 have the meanings of R18 and R19 given above and are identical to or different from them, R26 and R27 have the meanings of R10 and R11 given above and are identical to or different from them and/or cycloalkyl, phenyl and/or the heterocycles are optionally substituted by straight-chain or branched alkyl having up to 4 carbon atoms which is optionally substituted by hydroxyl, carboxyl, pyridyl, pyrimidyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, triazolyl or by groups of the formula -SO2-R31, -P(O)(OR32)(OR33) or -NR34R35, in which R31 has the meaning of R9 given above and is identical to or different from it, R32 and R33 have the meanings of R10 and R11 given above and are identical to or different from them, R34 and R35 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl or straight-chain or branched alkoxy having up to 3 carbon atoms, or R34 and R35 together with the nitrogen atom form a morpholinyl, triazolyl or thiomorpholinyl ring or a radical of the formula in which R36 represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 5 carbon atoms or straight-chain or branched alkyl having up to 4 carbon atoms which is optionally substituted by hydroxyl, or R3 and R4 together with the nitrogen atom form a morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl ring, or a radical of the formula in which R37 represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or represents straight-chain or branched alkyl having up to 5 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, trifluoromethyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by groups of the formula -(D)f -NR38R39, -CO-(CH2)g -O-CO-R40, -CO-(CH2)h -OR41 or -P(O)(OR42)(OR43), in which g and h are identical or different and each represents a number 1, 2 or
3, and f represents a number 0 or 1, D represents a group of the formula -CO or -SO2, R38 and R39 are identical or different and have the meanings of R7 and R8 given above, R40 represents straight-chain or branched alkyl having up to 4 carbon atoms, R41 represents straight-chain or branched alkyl having up to 4 carbon atoms, R42 and R43 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, or R37 represents a radical of the formula -(CO)i-E, in which i represents a number 0 or 1, E represents cyclopentyl, cyclohexyl, cycloheptyl, benzyl, phenyl, pyridyl, pyrimidyl or furyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of vitro, fluorine, chlorine, -SO3H, straight-chain or branched alkoxy having up to 4 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy or by a radical of the formula -SO2-NR444R45, in which R44 and R45 have the meanings of R18 and R19 given above and are identical to or different from them, or E represents radicals of the formulae and the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally mono- to trisubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 5 carbon atoms, nitro and groups of the formulae -P(O)(OR46)(OR47), or ~(CO)j NR49R50 in which R46 and R47 have the meanings of R10 and R11 given above and are identical to or different from them, R48 represents hydroxyl or straight-chain or branched alkoxy having up to 3 carbon atoms, j represents a number 0 or 1, and R49 and R50 are identical or different and have the meanings of R14 and R15 given above, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 5 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a radical of the formula -SO3H, -NR51R52 or -P(O)OR53OR54, in which R51 and R52 are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms, R53 and R54 are identical or different and have the meanings of R10 and R11 given above, and/or the alkyl is optionally substituted by phenyl which for its part may be mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, hydroxyl, straight-chain or branched alkoxy having up to 4 carbon atoms, or by a group of the formula -NR51'R52', in which R51' and R52' have the meanings of R51 and R52 given above and are identical to or different from them, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by phenyl, pyridyl, piperidinyl, pyrrolidinyl or tetrazolyl, optionally also attached via a nitrogen function, where the ring systems for their part may be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 5 carbon atoms, or R3 and R4 together with the nitrogen atom form radicals of the formulae R5 and R6 are identical or different and each represents hydrogen, hydroxyl or represents straight-chain or branched alkoxy having up to 4 carbon atoms, and their salts, hydrates, N-oxides and isomeric forms.

3. 2-Phenyl-substituted imidazotriazinones of the general formula (I) according to Claim 1 in which R1 represents straight-chain or branched alkyl having up to 3 carbon atoms, R2 represents straight-chain alkyl having up to 3 carbon atoms, R3 and R4 are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to
4 carbon atoms, or represents a straight-chain or branched alkyl chain having up to 6 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, straight-chain or branched alkoxycarbonyl having up to 4 carbon atoms, and/or by radicals of the formulae -SO3H, -(A)a-NR7R8; -O-CO-NR7'R8', -S(O)b-R9, -P(O)(OR10)(OR11), in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or SO2, R7, R7', R8 and R8' are identical or different and each represents hydrogen, or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl,~
piperidinyl and pyridyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, nitro, carboxyl, fluorine, chlorine, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a group of the formula -(SO2)c-NR12R13, in which c ~represents a number 0 or 1, R12 and R13 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, or R7, R7', R8 and R8' each represent methoxy, or represent straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, phenyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a group of the formula -(CO)d-NR14R15, in which R14 and R15 are identical or different and each represents hydrogen, methyl or ethyl, and d ~represents a number 0 or 1, or R7 and R8 and/or R7' and R8' together with the nitrogen atom form a morpholinyl, piperidinyl or triazolyl ring or radicals of the formulae ~
in which R16 represents hydrogen, phenyl, benzyl, morpholinyl, pyrrolidinyl, piperidinyl, piperazinyl or N-methylpiperazinyl, or represents straight-chain or, branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl, R9 represents methyl, R10 and R11 are identical or different and each represents hydrogen, methyl or ethyl, and/or the alkyl chain listed under R3/R4 is optionally substituted by cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, morpholinyl, furyl, tetrahydrofuranyl, or by radicals of the formulae in which R17 represents hydrogen, hydroxyl, formyl, acetyl or alkoxy having up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl or straight-chain or branched alkoxy having up to 3 carbon atoms, and where phenyl and the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, -SO3H, straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, hydroxyl, and/or by a radical of the formula -SO2NR18R19, in which R18 and R19 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and/or R3 or R4 represents a group of the formula -NR20R21, in which R20 and R21 have the meanings of R18 and R19 given above and are identical to or different from them, and/or R3 or R4 represents adamantyl, or represents radicals of the formulae or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl, morpholinyl, oxazolyl, thiazolyl, quinolyl, isoxazolyl, pyridyl, tetrahydrofuranyl, tetrahydropyranyl, or represents radicals of the formulae in which R22 has the meaning of R16 given above and is identical to or different from it, or represents formyl or acetyl, and where cycloalkyl, phenyl and/or the heterocycles are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, triazolyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 4 carbon atoms, nitro, and/or by groups of the formulae -SO3H, -OR23, (SO21)e NR24R25, -P(O)(OR26)(OR27), in which e ~represents a number 0 or 1, R23 ~represents a radical of the formula represents cyclopropyl, cyclopentyl, cyclobutyl or cyclohexyl, represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by cyclopropyl, cyclohexyl, benzyloxy, tetrahydropyranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, benzyloxycarbonyl or phenyl which for its part may be mono- or disubstituted by identical or different substituents selected from the group consisting of methoxy, hydroxyl, fluorine or chlorine, and/or where alkyl is optionally substituted by radicals of the formulae -CO-NR28R29 or -CO-R30, in which R28 and R29 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or R28 and R29 together with the nitrogen atom form a morpholinyl, pyrrolidinyl or piperidinyl ring, and R30 represents phenyl or adamantyl, R24 and R25 have the meaning of R18 and R19 given above and are identical to or different from them, R26 and R27 have the meanings of R10 and R11 given above and are identical to or different from them and/or cycloalkyl, phenyl and/or the heterocycles are optionally substituted by straight-chain or branched alkyl having up to 3 carbon atoms, which is optionally substituted by hydroxyl, carboxyl, pyridyl, pyrimidyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyi, triazolyl or by groups of the formula -SO2-R31, P(O)(OR32)(OR33) or -NR34R35, in which R31 represents methyl, R32 and R33 have the meanings of R10 and R11 given above and are identical to or different from them, R34 and R35 are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl or methoxy, or R34 and R35 together with the nitrogen atom form a morpholinyl, triazolyl or thiomorpholinyl ring or a radical of the formula in which R36 represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 3 carbon atoms or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl, or R3 and R4 together with the nitrogen atom form a morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl ring, or a radical of the formula in which R37 represents hydrogen, hydroxyl, formyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by groups of the formula -(D)f NR38R39, -CO-(CH2)g-O-CO-R40, -CO-(CH2)h-OR41 or -P(O)(OR42)(OR43), in which g and h are identical or different and each represents a number 1 or 2, and f represents a number 0 or 1, D represents a group of the formula -CO or -SO2, R38 and R39 are identical or different and have the meanings of R7 and R8 given above, R40 represents straight-chain or branched alkyl having up to 3 carbon atoms, R41 represents straight-chain or branched alkyl having up to 3 carbon atoms, R42 and R43 are identical or different and each represents hydrogen, methyl or ethyl, or R37 represents a radical of the formula -(CO)i-E, in which i ~represents a number 0 or 1, E ~represents cyclopentyl, benzyl, phenyl, pyridyl, pyrimidyl or furyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, -SO3H, straight-chain or branched alkoxy having up to 3 carbon atoms, hydroxyl, or by a radical of the formula -SO2-NR44R45, in which R44 and R45 have the meanings of R18 and R19 given above and are identical to or different from them, or E ~represents radicals of the formulae and the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally mono- to trisubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or groups of the formulae -P(O)(OR46)(OR47), =NR48 or ~(CO)i NR49R50 in which R46 and R47 have the meanings of R10 and R11 given above and are identical to or different from them, R48 represents hydroxyl or methoxy, j represents a number 0 or 1, and R49 and R50 are identical or different and have the meanings of R14 and R15 given above, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, cyclopropyl, cycloheptyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a radical of the formula -SO3H, -NR51R52 or P(O)OR53OR54, in which R51 and R52 are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, R53 and R54 are identical or different and have the meanings of R10 and R11 given above, and/or the alkyl is optionally substituted by phenyl which for its part may be mono- to disubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, hydroxyl, methoxy, or by a group of the formula -NR51'R52', in which R51' and R52' have the meanings of R51 and R52 given above and are identical to or different from them, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by phenyl, pyridyl, piperidinyl, pyrrolidinyl or tetrazolyl, if appropriate also attached via a nitrogen function, where the ring systems for their part may be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, or R3 and R4 together with the nitrogen atom form radicals of the formulae R5 and R6 are identical or different and each represents hydrogen, hydroxyl or represents straight-chain or branched alkoxy having up to 3 carbon atoms, and their salts, hydrates, N-oxides and isomeric forms.

4. 2-Phenyl-substituted imidazotriazinones of the general formula (I) according to Claim 1 in which R1 represents methyl or ethyl, R2 represents ethyl or propyl, R3 and R4 are identical or different and each represents a straight-chain or branched alkyl chain having up to 5 carbon atoms which is optionally substituted up to two times by identical or different substituents selected from the group consisting of hydroxyl and methoxy, or R3 and R4 together with the nitrogen atom form a piperidinyl, morpholinyl, thiomorpholinyl ring, or a radical of the formula in which R37 represents hydrogen, formyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by groups of the formulae -(D)f-NR38R39 or -P(O)(OR42)(OR43), in which f represents a number 0 or 1, D represents a group of the formula -CO, R38 and R39 are identical or different and each represents hydrogen or methyl, R42 and R43 are identical or different and each represents hydrogen, methyl or ethyl, or R37 represents cyclopentyl, and the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally mono- or disubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or groups of the formulae -P(O)(OR46)(OR47) or -(CO)i NR49R50, in which R46 and R47 are identical or different and each represents hydrogen, methyl or ethyl, j represents a number 0 or 1, and R49 and R50 are identical or different and each represents hydrogen or methyl and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, carboxyl, or by a radical of the formula P(O)OR53OR54, in which R53 and R54 are identical or different and each represents hydrogen, methyl or ethyl, and/or the heterocycles listed under R3 and R4, which are formed together with the nitrogen atom, are optionally substituted by pyrrolidinyl or piperidinyl attached via nitrogen, R5 represents hydrogen, and R6 represents ethoxy or propoxy, and their salts, hydrates, N-oxides and isomeric forms.
5. A 2-phenyl-substituted imidazotriazinone according to Claim 1 wherein R1 is methyl, R2 is n-propyl, the group NR3R4 forms a six-membered heterocycle containing a radical of the formula NR37 in which R37 is ethyl, the sulphonyl moiety is in the 5-position of the phenyl group, R5 is hydrogen and R6 is ethoxy in the 2-position of the phenyl group.
6. 2-Phenyl-substituted imidazotriazinones according to any one of Claims 1 to 5 having the following structures:

7. The compound 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one or a pharmaceutically acceptable salt thereof or a hydrate thereof or a hydrate of a pharmaceutically acceptable salt thereof.
8. The compound 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one in the form of a hydrochloride salt or a hydrate of a hydrochloride salt.
9. The compound 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one in the form of the monohydrochloride trihydrate.
10. 2-Phenyl-substituted imidazotriazinones of the general formula (I) according to any one of Claims 1 to 9 and pharmaceutically acceptable salts and hydrates thereof for the treatment of cardiovascular or cerebrovascular disorders or disorders of the urogenital system.
11. A pharmaceutical composition comprising a 2-phenyl-substituted imidazotriazinone according to any one of Claims 1 to 9, or a pharmaceutically acceptable salt or hydrate thereof, together with pharmacologically acceptable formulating agents.
12. A composition according to Claim 11 for the treatment of cardiovascular or cerebrovascular disorders or disorders of the urogenital system.
13. A composition according to Claim 11 for the treatment of erectile dysfunction.
14. Use of a 2-phenyl-substituted imidazotriazinone according to any one of Claims 1 to 9, or a pharmaceutically acceptable salt or hydrate thereof, for the treatment of cardiovascular or cerebrovascular disorders or disorders of the urogenital system.
15. Use of a 2-phenyl-substituted imidazotriazinone according to any one of Claims 1 to 9, or a pharmaceutically acceptable salt or hydrate thereof, for the treatment of erectile dysfunction.
16. Use of a 2-phenyl-substituted imidazotriazinone according to any one of Claims 1 to 9 or a pharmaceutically acceptable salt or hydrate thereof for the preparation of a pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disorders and disorders of the urogenital system.
17. Use according to Claim 16 for the preparation of a pharmaceutical composition, for the treatment of erectile dysfunction.
18. A pharmaceutical composition comprising 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one monohydro-chloride trihydrate, together with pharmacologically acceptable formulating agents.
19. Use of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one monohydrochloride trihydrate, for the treatment of cardiovascular or cerebrovascular disorders or disorders of the urogenital system.
20. Use of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one monohydrochloride trihydrate, for the treatment of erectile dysfunction.
21. ~Use of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one monohydrochloride trihydrate, in the manufacture of a pharmaceutical composition for the treatment of cardiovascular or cerebrovascular disorders or disorders of the urogenital system.
22. ~Use of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one monohydrochloride trihydrate, in the manufacture of a pharmaceutical composition for the treatment of erectile dysfunction.
23. ~A process for preparing 2-phenyl-substituted imidazotriazinones of formula (I) according to Claim 1, which process comprises reacting a compound of the general formula (V) in which R1, R2, R5 and R6 are as defined in Claim 1, with an amine of general formula (VI) HNR3R4 ~~(VI) in inert solvent, wherein R3 and R4 are as defined in Claim 1, followed, if required, by converting an obtained compound of formula (I) into a pharmaceutically acceptable salt, or a hydrate thereof, or a hydrate of a pharmaceutically acceptable salt thereof.
24. ~A process according to Claim 23 wherein the compound of formula (V) is obtained by reacting a compound of the general formula (II) in which R1 and R2 are each as defined in Claim 23 and L represents straight-chain or branched alkyl having up to 4 carbon atoms, with a compound of the general formula (III) in which R5 and R6 are each as defined in Claim 23, in a two-step reaction in the systems ethanol and phosphorus oxytrichloride/dichloroethane to form a compound of the general formula (IV) in which R1, R2, R5 and R6 are each as defined above, followed by reaction with chlorosulphonic acid to give the compound of the general formula (V).
25. Compounds of formula (V) wherein R1 represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, R2 represents straight-chain alkyl having up to 4 carbon atoms, and R5 and R6 are identical or different and each represents hydrogen straight-chain or branched alkyl having up to 6 carbon atoms or hydroxyl, or represents straight-chain or branched alkoxy having up to 6 carbon atoms.
26. Compounds according to Claim 25 in which R1 represents straight-chain or branched alkyl having up to 3 carbon atoms, R2 represents straight-chain alkyl having up to 3 carbon atoms and R5 and R6 are identical or different and each represents hydrogen, hydroxyl or straight-chain or branched alkoxy having up to 4 carbon atoms.
27. Compounds according to Claim 25 in which R5 and R6 are identical or different and each represents straight-chain or alkoxy having up to 3 carbon atoms.
28. Compounds according to Claim 25 in which R1 represents methyl or ethyl, R2 represents ethyl or propyl, R5 represents hydrogen and R6 is ethoxy or propoxy.
29. ~A process for preparing 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one which comprises reacting 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride with N-ethyl-piperazine.
30. A process according to Claim 29 which comprises the further step of crystallizing the product from a mixture of an organic solvent and dilute aqueous hydrochloric acid to obtain the product in the form of the hydrochloride trihydrate.
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