2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors

• US 6,362,178 B1
• Filed: 07/21/2000
• Issued: 03/26/2002
• Est. Priority Date: 11/12/1997
• Status: Expired due to Term

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer AG
• Inventors: Keldenich, Jörg, Perzborn, Elisabeth, Schlemmer, Karl-Heinz, Es-Sayed, Mazen, Serno, Peter, Dembowsky, Klaus, Haning, Helmut, Schenke, Thomas, Niewöhner, Ulrich, Nowakowski, Marc, Bischoff, Erwin
• Primary Examiner(s): Kifle, Bruck
• Application Number:
  US09/554,162
• Time in Patent Office: 613 Days
• Field of Search: 540/569, 540/575, 544/112, 544/184, 514/81, 514/218, 514/221, 514/228.5, 514/233.2, 514/243
• US Class Current: 514/218
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07F 9/6561 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

1. A compound of the 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—

NR^7′

R^8′

, —

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, R^7′

, R⁸ and R^8′

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, R^7′

, R⁸ and R^8′

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 R^7′

and R^8′

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)_eNR²⁴R²⁵, —

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 1, 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),

 

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 —

NR^51′

R^52′

, in which

R^51′

and R^52′

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 structural isomers.

2. A compound of the 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—

NR^7′

R^8′

, —

S(O)_b—

R⁹, 13 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, R^7′

, R⁸ and R^8′

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, R^7′

, R⁸ and R^8′

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 R^7′

and R^8′

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 —

SO₂—

NR¹⁸R¹⁹, 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)_eNR²⁴R²⁵, —

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 nitro, 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—

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 5 carbon atoms, nitro and groups of the formulae —

P(O)(OR⁴⁶)(OR⁴⁷),

 

═

NR⁴⁸ or —

(CO)_jNR⁴⁹R⁵⁰ 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)OR⁵³R⁵⁴, 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 —

NR^51′

R^52′

, in which

R^51′

and R^52′

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 structural isomers.

3. A compound of the 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—

NR^7′

R^8′

, —

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, R^7′

, R⁸ and R^8′

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, R^7′

, R⁸ and R^8′

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 R^7′

and R^8′

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 —

SO₂—

NR¹⁸R¹⁹, 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, (SO₂)_eNR²⁴R²⁵, —

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, tetrahydrofuranyl, 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)_jNR⁴⁹R⁵⁰ 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 —

NR^51′

R^52′

, in which

R^51′

and R^52′

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 structural isomers.

4. A compound of the 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)_jNR⁴⁹R⁵⁰, 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 compound of the according to claim 1 having the following structures:

6. Process for preparing a compound according to claim 1, characterized in that initially compounds of the formula (II)

in which

R¹ and R² are each as defined above in claim 1, and

L represents straight-chain or branched alkyl having up to 4 carbon atoms,

are converted with compounds of the general formula (III)

in which

R⁵ and R⁶ are each as defined above in claim 1,

in a two-step reaction first in the system consisting of ethanol and second in the system consisting of phosphorus oxytrichloride/dichloroethane into the compounds of the general formula (IV)

in which

R¹, R², R⁵ and R⁶ are each as defined above in claim 1,

which are reacted in a further step with chlorosulphonic acid to give the compounds of the formula (V)

in which

R¹, R², R⁵ and R⁶ are each as defined above in claim 1,

which are finally reacted with amines of the formula (VI)

7. Pharmaceuticals which comprise at least one 2-phenyl-substituted imidazotriazinone according to claim 1 and pharmacologically acceptable formulating agents.

8. A method of treating chronic heart failure or erectile dysfunction, comprising administering to a mammal an effective amount of a compound according to claim 1.