Novel substituted pyrazole derivatives

Abstract

The present invention relates to novel substituted pyrazole derivatives of the general formula (I) in which R 1 , R 2 , R 3 and A are each as defined, and to processes for their preparation and to their use as medicaments, in particular as medicaments for the treatment of cardiovascular disorders.

1 . A compound of the formula (I)  
       
         
           
           
               
               
           
         
       
       in which 
 R 1  represents a saturated or aromatic 5- or 6-membered heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, which may be attached via a nitrogen atom, 
 and which is optionally substituted up to 2 times by identical or different radicals from the group (i) consisting of 
 hydrogen, amino, azido, formyl, mercaptyl, carboxyl, hydroxyl, straight-chain or branched acyl, alkoxy, alkylthio or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro, cyano, halogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms which for its part may be substituted by hydroxyl, amino, azido, carboxyl, straight-chain or branched acyl, alkoxy, alkoxycarbonyl or acylamino having in each case up to 5 carbon atoms or by a radical of the formula —OR 4  
 in which  
 R 4  represents straight-chain or branched acyl having up to 5 carbon atoms  
 
 
 and/or is substituted by a radical of the formula  
                     
 or  
 —S(O) c —NR 6 R 7  
 in which  
 a, b and b′ are identical or different and each represents a number 0, 1, 2 or 3,  
 R 5  is hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms,  
 c is a number 1 or 2 and  
 R 6  and R 7  are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 10 carbon atoms which is optionally substituted by cycloalkyl having 3 to 8 carbon atoms or by aryl having 6 to 10 carbon atoms which for its part may be substituted by halogen, 
 or  
 represents aryl having 6 to 10 carbon atoms which is optionally substituted by halogen,  
 or  
 represents cycloalkyl having 3 to 7 carbon atoms,  
 or  
 
 R 6  and R 7  together with the nitrogen atom form a 5- to 7-membered saturated heterocycle which may optionally contain a further oxygen atom or a radical —NR 8  
 in which  
 R 8  represents hydrogen, straight-chain or branched alkyl having up to 4 carbon atoms or a radical of the formula  
                     
 or benzyl or phenyl where the ring systems are optionally substituted by halogen,  
 
 
 
 and which is substituted by at least one radical from the group (ii) consisting of 
 a 3- to 8-membered ring which may be saturated, unsaturated or partially unsaturated, contains 1 to 4 heteroatoms from the group consisting of N, O, and S, said S heteroatoms optionally bearing 1 or 2 oxygens, and which may also be attached via N,  
 and which is optionally mono- or polysubstituted by a 5- or 6-membered ring which contains two oxygen atoms as ring members and forms a bicyclic unit or a spiro unit with the 3- to 8-membered ring, and/or by hydroxyl, cyano, straight-chain or branched alkyl, acyl or alkoxycarbonyl having in each case up to 6 carbon atoms, where alkyl, acyl and alkoxycarbonyl may be substituted by hydroxyl, amino, halogen, carboxyl, straight-chain or branched acyl, alkoxy, alkoxycarbonyl or acylamino having in each case up to 5 carbon atoms, and  
 an aryl ring having 6 to 10 carbon atoms which is substituted by straight-chain or branched alkyl having up to 4 carbon atoms,  
 and  
 (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkinyl, (C 7 -C 20 )alkyl, which is optionally substituted by aryl, heteroaryl, halogen, cyano, dialkylamino, cycloalkyl, alkylamine, hydroxyl, amino, azido, carboxyl, straight-chain or branched acyl, alkoxy, alkoxycarbonyl or acylamino having in each case up to 5 carbon atoms or by a radical of the formula —OR 4  
 in which  
 R 4  represents straight-chain or branched acyl having up to 5 carbon atoms  
 
 and  
 (C 1 -C 6 )alkyl which is substituted 1- to 3 times by aryl, heteroaryl, halogen(s), cyano, dialkylamino, alkylamino or cycloalkyl  
 and  
 acyl, which is substituted by halogen(s), or by acyloxy, arylthio or heteroarylthio,  
 and  
 —NO or radicals of the formulae —SO 3 H and —S(O) d R 9 ,  
 in which  
 d represents a number 1 or 2, 
 R 9  represents straight-chain or branched alkyl having 1 to 10 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or an unsaturated 5- to 6-membered heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, where the ring systems may optionally be substituted by halogen or by straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms,  
 
 
 and 
 a radical of the formula PO(OR 10 )(OR 11 )  
 in which 
 R 10  and R 11  are identical or different and each represents hydrogen, straight-chain or branched alkyl having up to 8 carbon atoms or cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or benzyl,  
 
 and  
 oxycycloalkyl having 3 to 8 ring members or radicals of the formulae —CON═C(NH 2 ) 2 , —C═NH(NH 2 ), —NH—C(═NH)NH 2  or (CO) e NR 12 R 13    
 in which 
 e represents a number 0 or 1,  
 R 12  and R 13  are identical or different and each represents hydrogen, straight-chain or branched alkyl having up to 14 carbon atoms or cycloalkyl having 3 to 14 carbon atoms, aryl having 6 to 10 carbon atoms or a saturated or unsaturated 3- to 10-membered ring having up to 5 heteroatoms from the group consisting of N, O, S, where the abovementioned radicals may optionally be substituted by aryl having 6 to 10 carbon atoms, heterocyclyl, cycloalkyl having 3 to 7 carbon atoms, hydroxyl, amino or straight-chain or branched alkoxy, acyl or alkoxycarbonyl having in each case up to 6 carbon atoms,  
 and, in the case that e=1,  
 R 12  and R 13 , together with the nitrogen atom to which they are attached, may also form a 5- or 6-membered ring having up to 3 heteroatoms from the group consisting of N, O, S, which may optionally be substituted up to 3 times by hydroxyl, alkoxy or alkyl having in each case up to 8 carbon atoms,  
 and, in the case that e=0,  
 R 12  and R 13  may also represent straight-chain, branched or cyclic acyl having up to 14 carbon atoms, hydroxyalkyl, straight-chain or branched alkoxycarbonyl or acyloxyalkyl having in each case up to 6 carbon atoms, or a radical of the formula —SO 2 R 14    
 in which  
 R 14  represents straight-chain or branched alkyl having up to 4 carbon atoms,  
 
 and/or  
 R 12  and R 13  also represent radicals of the formulae  
                     
 in which R 15 -R 16  and R 18 -R 31  are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms,  
 g represents a number 0, 1 or 2,  
 and  
 R 17  represents phenyl, straight-chain or branched alkyl having up to 6 carbon atoms or cycloalkyl having 3 to 8 carbon atoms,  
 with the proviso that, if e=0, R 12  and R 13  do not simultaneously represent hydrogen,  
 
 or  
 R 1  represents a purine radical which may optionally be substituted up to three times by halogen, azido, cyano, hydroxyl, amino, monoalkylamino having up to 5 carbon atoms, dialkylamino having in each case up to 5 carbon atoms, alkyl having up to 5 carbon atoms and/or alkoxy having up to 5 carbon atoms,  
 R 2  and R 3 , together with the double bond, form a 6-membered saturated or aromatic heterocycle having up to 3 heteroatoms from the group consisting of N, S and O, 
 which is optionally substituted up to three times by identical or different substituents from the group consisting of formyl, carboxyl, hydroxyl, mercaptyl, straight-chain or branched acyl, alkylthio or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro, cyano, halogen or straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms which for its part may be substituted by hydroxyl, amino, carboxyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 5 carbon atoms,  
 and/or which is optionally substituted by a group of the formula —NR 32 R 33    
 in which 
 R 32  and R 33  are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms,  
 or  
 
 
 R 32  represents hydrogen and  
 R 33  represents acyl,  
 and/or which is optionally substituted by phenyl which for its part may be substituted up to 2 times by identical or different substituents from the group consisting of halogen and straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms,  
 and/or which is optionally substituted by a group of the formula —N═CH—NR 34 R 35  
 in which  
 
 R 34  and R 35  are identical or different and each represents hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms,  
 A represents a 5- or 6-membered aromatic or saturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and O or represents phenyl, 
 which are optionally substituted up to 3 times by identical or different substituents from the group consisting of amino, mercaptyl, hydroxyl, formyl, carboxyl, straight-chain or branched acyl, alkylthio, alkyloxyacyl, alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro, cyano, trifluoromethyl, azido, halogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms which for its part may be substituted by hydroxyl, carboxyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 5 carbon atoms,  
 and/or is substituted by a group of the formula —(CO) h —NR 36 R 37    
 in which 
 h represents a number 0 or 1,  
 R 36  and R 37  are identical or different and each represents hydrogen, phenyl, benzyl or straight-chain or branched alkyl or acyl having in each case up to 5 carbon atoms,  
 or a stereoisomeric form or salt thereof.  
 
 
 
     
     
         2 . The compound of formula (I) according to  claim 1   
       in which 
 R 1  represents a saturated or aromatic 6-membered heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, which may be attached via a nitrogen atom, 
 and which is optionally substituted up to 2 times by identical or different radicals from the group (i) consisting of 
 hydrogen, amino, azido, formyl, mercaptyl, carboxyl, hydroxyl, straight-chain or branched acyl, alkoxy, alkylthio or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro, cyano, halogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms which for its part may be substituted by hydroxyl, amino, azido, carboxyl, straight-chain or branched acyl, alkoxy, alkoxycarbonyl or acylamino having in each case up to 5 carbon atoms or by a radical of the formula —OR 4  
 in which  
 R 4  represents straight-chain or branched acyl having up to 5 carbon atoms  
 
 
 and/or is substituted by a radical of the formula  
                     in which    a, b and b′ are identical or different and each represents a number 0, 1, 2 or 3, 
 R 5  is hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms,  
   
 
 and which is substituted by at least one radical from the group (ii) consisting of 
 a 3- to 8-membered ring which may be saturated, unsaturated or partially unsaturated, contains 1 to 4 heteroatoms from the group consisting of N, O, and S, said S heteroatoms optionally bearing 1 or 2 oxygens and which may also be attached via N,  
 and which is optionally mono- or polysubstituted by a 5- or 6-membered ring which contains two oxygen atoms as ring members and forms a bicyclic unit or a spiro unit with the 3- to 8-membered ring, and/or by hydroxyl, cyano, straight-chain or branched alkyl, acyl or alkoxycarbonyl having in each case up to 6 carbon atoms, where alkyl, acyl and alkoxycarbonyl may be substituted by hydroxyl, amino, halogen, carboxyl, straight-chain or branched acyl, alkoxy, alkoxycarbonyl or acylamino having in each case up to 5 carbon atoms,  
 and  
 an aryl ring having 6 to 10 carbon atoms which is substituted by straight-chain or branched alkyl having up to 4 carbon atoms,  
 and  
 (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkinyl, (C 7 -C 20 )alkyl, which is optionally substituted by aryl, heteroaryl, halogen, cyano, dialkylamino, cycloalkyl, alkylamine, hydroxyl, amino, azido, carboxyl, straight-chain or branched acyl, alkoxy, alkoxycarbonyl or acylamino having in each case up to 5 carbon atoms or by a radical of the formula —OR 4  
 in which  
 R 4  represents straight-chain or branched acyl having up to 5 carbon atoms  
 
 and  
 (C 1 -C 6 )alkyl which is substituted 1- to 3 times by aryl, heteroaryl, halogen(s), cyano, dialkylamino, alkylamino or cycloalkyl  
 and  
 acyl, which is substituted by halogen(s), or by acyloxy, arylthio or heteroarylthio,  
 and  
 —NO or radicals of the formulae —SO 3 H and —S(O) d R 9 ,  
 in which  
 d represents a number 1 or 2, 
 R 9  represents straight-chain or branched alkyl having 1 to 10 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or an unsaturated 5- to 6-membered heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, where the ring systems may optionally be substituted by halogen or by straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms,  
 
 
 and 
 a radical of the formula PO(OR 10 )(OR 11 )  
 in which 
 R 10  and R 11  are identical or different and each represents hydrogen, straight-chain or branched alkyl having up to 8 carbon atoms or cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or benzyl,  
 
 and  
 oxycycloalkyl having 3 to 8 ring members or radicals of the formulae —CON═C(NH 2 ) 2 , —C═NH(NH 2 ), —NH—C(═NH)NH 2  or (CO) e NR 12 R 13    
 in which 
 e represents a number 0 or 1,  
 R 12  and R 13  are identical or different and each represents hydrogen, straight-chain or branched alkyl having up to 14 carbon atoms or cycloalkyl having 3 to 14 carbon atoms, aryl having 6 to 10 carbon atoms or a saturated or unsaturated 3- to 10-membered ring having up to 5 heteroatoms from the group consisting of N, O, S, where the abovementioned radicals may optionally be substituted by aryl having 6 to 10 carbon atoms, heterocyclyl, cycloalkyl having 3 to 7 carbon atoms, hydroxyl, amino or straight-chain or branched alkoxy, acyl or alkoxycarbonyl having in each case up to 6 carbon atoms,  
 and, in the case that e=1,  
 R 12  and R 13 , together with the nitrogen atom to which they are attached, may also form a 5- or 6-membered ring having up to 3 heteroatoms from the group consisting of N, O, S, which may optionally substituted up to 3 times by hydroxyl, alkoxy or alkyl having in each case up to 8 carbon atoms,  
 and, in the case that e=0,  
 R 12  and R 13  may also represent straight-chain, branched or cyclic acyl having up to 14 carbon atoms, hydroxyalkyl, straight-chain or branched alkoxycarbonyl or acyloxyalkyl having in each case up to 6 carbon atoms, or a radical of the formula —SO 2 R 14  
 in which  
 R 14  represents straight-chain or branched alkyl having up to 4 carbon atoms,  
 
 and/or  
 R 12  and R 13  also represent radicals of the formulae  
                     
 in which  
 R 15 -R 16  and R 18 -R 31  are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms,  
 g represents a number 0, 1 or 2,  
 and  
 R 17  represents phenyl, straight-chain or branched alkyl having up to 6 carbon atoms or cycloalkyl having 3 to 8 carbon atoms,  
 with the proviso that, if e=0, R 12  and R 13  do not simultaneously represent hydrogen,  
 
 
 or  
 R 1  represents a purine radical which may optionally be substituted up to three times by halogen, azido, cyano, hydroxyl, amino, monoalkylamino having up to 5 carbon atoms, dialkylamino having in each case up to 5 carbon atoms, alkyl having up to 5 carbon atoms and/or alkoxy having up to 5 carbon atoms,  
 R 2  and R 3 , together with the double bond, form a fused pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl ring, 
 which are optionally substituted up to 2 times by identical or different substituents from the group consisting of formyl, carboxyl, hydroxyl, mercaptyl, straight-chain or branched acyl, alkylthio or alkoxycarbonyl having in each case up to 5 carbon atoms, nitro, cyano, azido, fluorine, chlorine, bromine or straight-chain or branched alkyl or alkoxy having in each case up to 5 carbon atoms which for its part may be substituted by hydroxyl, amino, carboxyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms,  
 and/or  
 the abovementioned heterocyclic rings are optionally substituted by a group of the formula —NR 32 R 33  
 in which  
 R 32  and R 33  are identical or different and represent hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms  
 or  
 R 32  represents hydrogen  
 and  
 
 
 R 33  represents formyl  
 and/or the abovementioned fused pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl rings are optionally substituted by phenyl which for its part may be substituted by fluorine, chlorine, bromine or by straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms,  
 A represents thienyl, tetrahydropyranyl, tetrahydrofuranyl, phenyl, morpholinyl, pyrimidyl, pyrazinyl, pyridazinyl or pyridyl which are optionally substituted up to 2 times by identical or different substituents from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl, alkylthio, alkyloxyacyl, alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, fluorine, chlorine and bromine,  
 or a stereoisomeric form or salt thereof.  
 
     
     
         3 . The compound of formula (I) according to  claim 1   
       in which 
 R 1  represents a pyrimidine radical 
 which is optionally substituted up to 2 times by identical or different radicals from the group (i) consisting of 
 hydrogen, amino, hydroxyl, alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, cyano or halogen,  
 
 
 and which is substituted by at least one radical from the group (ii) consisting of 
 a 5- to 6-membered ring which may be saturated, unsaturated or partially unsaturated, which contains 1 to 3 heteroatoms from the group consisting of N, O, and S, said S heteroatoms optionally bearing 1 or 2 oxygens, and which may also be attached via N,  
 and which is optionally mono- or polysubstituted by a 5-membered ring which contains two oxygen atoms as ring members and which forms, with the 3- to 8-membered ring, a bicyclic unit or a spiro unit, such as, for example, a 1,4-dioxa-8-azaspiro[4.5]decane or 1.5-dioxa-9-azaspiro[5.5]undecane radical, and/or by hydroxyl, cyano, straight-chain or branched alkyl, acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, where alkyl, acyl and alkoxycarbonyl may be substituted by hydroxyl, amino, halogen, carboxyl, straight-chain or branched acyl or alkoxy having in each case up to 3 carbon atoms,  
 and  
 a tolyl radical,  
 and  
 C 7 -alkyl which is optionally substituted by cyano,  
 and  
 (C 1 -C 5 )alkyl, which is 1- to 3-times substituted by halogen(s), cyano, aryl and acyloxy,  
 and  
 —NO or radicals of the formula —S(O) d R 9 ,  
 in which  
 d represents a number 1 or 2, 
 R 9  represents straight-chain or branched alkyl having 1 to 4 carbon atoms, aryl having 6 carbon atoms or thienyl,  
 
 
 and 
 a radical of the formula PO(OR 10 )(OR 11 ),  
 in which 
 R 10  and R 11  are identical or different and each represents straight-chain or branched alkyl having up to 3 carbon atoms,  
 
 and  
 radicals of the formulae —NH—C(═NH)NH 2  and (CO) e NR 12 R 13    
 in which 
 e represents a number 0 or 1,  
 R 12  and R 13  are identical or different and each represents hydrogen, straight-chain or branched alkyl having up to 4 carbon atoms or cycloalkyl having 3 carbon atoms, where the abovementioned radicals may optionally be substituted by aryl having 6 carbon atoms, furyl, cycloalkyl having 3 carbon atoms, hydroxyl, straight-chain alkoxy having up to 2 carbon atoms,  
 and, in the case that e=1,  
 R 12  and R 13 , together with the nitrogen atom to which they are attached, may also form a 5- or 6-membered ring having up to 2 heteroatoms from the group consisting of N, O, S which may optionally be substituted up to 2 times by hydroxyl or methyl,  
 and, in the case that e=0,  
 R 12  and R 13  may also represent straight-chain acyl having up to 14 carbon atoms,  
 and/or  
 R 12  and R 13  also represent a radical of the formula  
                     
 with the proviso that in the case that e=0, R 12  and R 13  do not simultaneously represent hydrogen,  
 
 
 or  
 R 1  represents a purine radical which may optionally be substituted up to two times by halogen, azido, amino, monoalkylamino having up to 4 carbon atoms and/or methyl,  
 R 2  and R 3  together with the double bond form a pyridyl or pyrimidinyl ring,  
 A represents phenyl or pyrimidyl, which are optionally substituted by fluorine, chlorine or bromine,  
 or a stereoisomeric form or salt thereof.  
 
     
     
         4 . The compound according to  claim 1   
       where 
 R 1  represents a radical of the formula  
                     
 in which  
 R′ represents NH 2 ,  
 R″ represents optionally substituted morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, triazolyl or thiomorpholinyl  
 and  
 R′″ represents hydrogen or NH 2 .  
 
     
     
         5 . The compound according to  claim 4  in which R″ represents morpholinyl.  
     
     
         6 . A process for preparing the compounds of the formula (I) according to  claim 1 ,  
       characterized in that  
       depending on the various meanings of the heterocycles listed above under R 2  and R 3  
 [A] a compound of the formula 
 R 1 —D  (II) in which    R 1  is as defined above in  claim 1     and    D represents a radical selected from the formulae                          in which    R 38  represents C 1 -C 4 -alkyl    is converted, by reaction with a compound of the formula (III)   A—CH 2 —NH—NH 2   (III)   in which    A is as defined above in  claim 1     in inert solvent, if appropriate in the presence of a base, into a compound of the formula (IV) or (IVa)                          in which    A and R 1  are each as defined above in  claim 1 ,    and, in the case of the compound of the formula (IVa), is subsequently cyclized with a carboxylic acid, nitrile, formamide or guanidium salt,    and, in the case of the compound of the formula (IV), is cyclized with a 1,3-dicarbonyl derivative, its salt, tautomer, enol ether or enamine, in the presence of acid,    
 or  
 [B] in the case that R 2  and R 3  together form a pyrazine ring, a compound of the formula (IV) is initially converted by nitrosation into a compound of the formula (V)  
                     in which    A and R 1  are each as defined above, in  claim 1     in a second step, compound of the formula (VI)                          in which    A and R 1  are each as defined above in  claim 1     is prepared by a reduction,    and these are this is subsequently cyclized with a 1,2-dicarbonyl compound,    
 or  
 [C] a compound of the formula (VII)  
                     in which    A 1 , R 2  and R 3  are each as defined above in  claim 1     and    L represents a radical of the formula —SnR 39 R 40 R 41 , ZnR 42 , iodine, bromine or triflate    in which 
 R 39 , R 40  and R 41  are identical or different and each represents straight-chain or branched alkyl having up to 4 carbon atoms  
   
 and 
 R 42  represents halogen  
 is reacted with a compound of the formula (VIII) 
 R 1 —T  (VIII), 
 
 in which  
 R 1  is as defined above in  claim 1   
 and  
 in the case that L=SnR 39 R 40 R 41  or ZnR 42 ,  
 T represents triflate or represents halogen,  
 and,  
 in the case that L=iodine, bromine or triflate,  
 T represents a radical of the formula SnR 39′ R 40′ R 41′ , ZnR 42′  or BR 43′ R 44′   
 in which 
 R 39′ , R 40′ , R 41′  and R 42′  have the meanings of R 39 , R 40 , R 41  and R 42  given above and are identical to or different from them,  
 
 R 43′  and R 44′  are identical or different and each represents hydroxyl, aryloxy having 6 to 10 carbon atoms or straight-chain or branched alkyl or alkoxy having in each case up to 5 carbon atoms, or together form a 5- or 6-membered carbocyclic ring  
 in a palladium-catalysed reaction in inert solvent,  
 or  
 [D] in the case that R 1  represents an optionally substituted pyrimidine radical, an amidine of the formula (IX)  
                     in which    A, R 2  and R 3  are each as defined above in  claim 1     is reacted with a compound of the formula (X), (Xa), (Xb) or (Xc)                          in which    R 1′  represents the optionally substituted cycloalkyl radical listed above under R 1 ;    Alk represents straight-chain or branched alkyl having up to 8 carbon atoms,    and    Z represents an NH 2  group, a monoalkylamino group having up to 7 carbon atoms, a dialkylamino group having up to 7 carbon atoms, a piperidinyl or morpholinyl radical which is attached via the nitrogen, hydroxyl, alkoxy having up to 7 carbon atoms, acyloxy having up to 7 carbon atoms or aroyloxy having 6 to 10 carbon atoms,    and, in the case of the groups —S(O) c NR 6 R 7  and —S(O) c′ NR 6′ R 7′ , starting from the unsubstituted compound of the formula (I), reacted initially with thionyl chloride and, in a second step, with an appropriate amine    and, if appropriate, the substituents listed under X, Y, R 1 , R 2 , R 3  and/or R 4  are modified or introduced by acylation of free amino groups or hydroxyl groups, chlorination, catalytic hydrogenation, reduction, oxidation, removal of protective groups and/or nucleophilic substitution.    
 
     
     
         7 . A pharmaceutical composition comprising a compound of the formula (I) according to  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         8 . Cancelled  
     
     
         9 . A pharmaceutical composition comprising at least one compound of the general formula (I) according to  claim 1  in combination with an organic nitrate or NO donor.  
     
     
         10 . A pharmaceutical composition comprising at least one compound of the formula (I) according to  claim 1  in combination with a compound which inhibits the degradation of cyclic guanosine monophosphate (cGMP).  
     
     
         11 . Cancelled  
     
     
         12 . A method for treating a cardiovascular disease comprising administering to a mammal an effective amount of a compound according to  claim 1 .  
     
     
         13 . The method of  claim 12 , wherein said cardiovascular disease is hypertension.  
     
     
         14 . A method of treating thromboembolic disorders and ischemia comprising administering to a mammal an effective amount of a compound according to  claim 1 .  
     
     
         15 . A method of treating sexual dysfunction comprising administering to a mammal an effective amount of a compound according to  claim 1 .  
     
     
         16 . A method of treating inflammation comprising administering to a mammal an effective amount of a compound according to  claim 1 .  
     
     
         17 . The method of  claim 12 ,  13 ,  14 ,  15 , or  16  wherein the a compound of the general formula (I) according to  claim 1  is administered in combination with an organic nitrate or NO donor.  
     
     
         18 . The compound of  claim 1 , wherein when said radical from group (ii) is a 3- to 8-membered ring, this ring is selected from the group consisting of imidazolyl, imidazolinyl, imidazolidinyl, morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, triazolyl, pyrrolyl, thiomorpholinyl, S-oxothiomorpholinyl and S,S-dioxothiomorpholinyl.  
     
     
         19 . The compound of  claim 2 , wherein when said radical from group (ii) is a 3- to 8-membered ring, this ring is selected from the group consisting of imidazolyl, imidazolinyl, imidazolidinyl, morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, triazolyl, pyrrolyl, thiomorpholinyl, S-oxothiomorpholinyl and S,S-dioxothiomorpholinyl.  
     
     
         20 . The compound of  claim 3 , wherein when said radical from group (ii) is a 5- to 6-membered ring, this ring is selected from the group consisting of imidazolyl, imidazolinyl, imidazolidinyl, morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, triazolyl, pyrrolyl and thiomorpholinyl.  
     
     
         21 . The process of  claim 6 , wherein when said compound of the general formula (IV) is cyclized with a 1,3-dicarbonyl derivative, its salt, tautomer, enol ether or enamine in the presence of acid, this is carried out under microwave radiation.  
     
     
         22  The process of  claim 6  wherein in part [B] the 1,2-dicarbonyl compound used in said cyclization with the compound of formula (VI) is aqueous glyoxal solution.  
     
     
         23 . The method of  claim 12 ,  13 ,  14 ,  15  or  16  wherein the compounds of general formula (I) according to  claim 1  are administered in combination with a compound which inhibits the degradation of cyclic guanosine monophosphate (cGMP).