Alkylamine-substituted dicyanopyridine and amino acid ester prodrugs thereof

Abstract

The present application relates to novel 6-alkylamino-substituted dicyanopyridines, to their amino acid ester prodrugs, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, preferably for the treatment and/or prevention of cardiovascular disorders.

1 - 10 . (canceled) 
     
     
         11 . A compound of formula (XIII): 
       
         
           
           
               
               
           
         
         in which 
         R 1  represents hydrogen or (C 1 -C 4 )-alkyl, 
         R 2  represents (C 1 -C 6 )-alkyl, (C 2 -C 4 )-alkenyl, (C 2 -C 4 )-alkynyl or (C 3 -C 7 )-cycloalkyl, 
         where (C 1 -C 6 )-alkyl may be substituted by 1 to 3 substituents selected independently of one another from the group consisting of fluorine, chlorine, trifluoromethyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, (C 3 -C 7 )-cycloalkyl, (C 3 -C 7 )-cycloalkoxy, (C 1 -C 4 )-alkylsulfanyl and (C 1 -C 4 )-alkylsulfonyl, 
         and 
         where (C 2 -C 4 )-alkenyl and (C 2 -C 4 )-alkynyl may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         and 
         where (C 3 -C 7 )-cycloalkyl may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, chlorine, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         or 
         R 1  and R 2  together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle which may contain a further heteroatom from the group consisting of N, O and S, 
         where the 4- to 7-membered heterocycle may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, chlorine, oxo, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         R 8  represents hydrogen or the side group of a natural α-amino acid or its homologs or isomers, 
         R 9  represents hydrogen or methyl, 
         R 10  represents hydrogen or methyl, 
         R 11  represents hydrogen or the side group of a natural α-amino acid or its homologs or isomers, 
         R 12  represents hydrogen or methyl, 
         R 13A  represents hydrogen, (C 1 -C 4 )-alkyl, or an amino protective group, 
         R 14A  represents hydrogen or (C 1 -C 4 )-alkyl, or an amino protective group, 
         or 
         R 13A  and R 14A  together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycle, 
         where the 5- or 6-membered heterocycle may be substituted by 1 or 2 substituents independently selected from the group consisting of (C 1 -C 4 )-alkyl, amino, hydroxyl and (C 1 -C 4 )-alkoxy, 
         or 
         R 14A  together with R 11  and the atoms, to which they are attached, forms a pyrrolidine or piperidine ring, 
         or a salt thereof. 
       
     
     
         12 . A compound of formula (XIV): 
       
         
           
           
               
               
           
         
         L 1  represents (C 2 -C 6 )-alkanediyl, 
         R 1  represents hydrogen or (C 1 -C 4 )-alkyl, 
         R 2  represents (C 1 -C 6 )-alkyl, (C 2 -C 4 )-alkenyl, (C 2 -C 4 )-alkynyl or (C 3 -C 7 )-cycloalkyl, 
         where (C 1 -C 6 )-alkyl may be substituted by 1 to 3 substituents selected independently of one another from the group consisting of fluorine, chlorine, trifluoromethyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, (C 3 -C 7 )-cycloalkyl, (C 3 -C 7 )-cycloalkoxy, (C 1 -C 4 )-alkylsulfanyl and (C 1 -C 4 )-alkylsulfonyl, 
         and 
         where (C 2 -C 4 )-alkenyl and (C 2 -C 4 )-alkynyl may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         and 
         where (C 3 -C 7 )-cycloalkyl may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, chlorine, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         or 
         R 1  and R 2  together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle which may contain a further heteroatom from the group consisting of N, O and S, 
         where the 4- to 7-membered heterocycle may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, chlorine, oxo, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         R 8  represents hydrogen or the side group of a natural α-amino acid or its homologs or isomers, 
         R 9  represents hydrogen or methyl, 
         R 10  represents hydrogen or methyl, 
         R 15A  represents hydrogen, (C 1 -C 4 )-alkyl, or an amino protective group, 
         R 16A  represents hydrogen or (C 1 -C 4 )-alkyl, or an amino protective group, 
         or 
         R 15A  and R 16A  together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycle, 
         where the 5- or 6-membered heterocycle may be substituted by 1 or 2 substituents independently selected from the group consisting of (C 1 -C 4 )-alkyl, amino, hydroxyl and (C 1 -C 4 )-alkoxy, 
         or a salt thereof. 
       
     
     
         13 . A compound of formula (XV): 
       
         
           
           
               
               
           
         
         L 2  represents (C 2 -C 6 )-alkanediyl, 
         R 1  represents hydrogen or (C 1 -C 4 )-alkyl, 
         R 2  represents (C 1 -C 6 )-alkyl, (C 2 -C 4 )-alkenyl, (C 2 -C 4 )-alkynyl or (C 3 -C 7 )-cycloalkyl, 
         where (C 1 -C 6 )-alkyl may be substituted by 1 to 3 substituents selected independently of one another from the group consisting of fluorine, chlorine, trifluoromethyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, (C 3 -C 7 )-cycloalkyl, (C 3 -C 7 )-cycloalkoxy, (C 1 -C 4 )-alkylsulfanyl and (C 1 -C 4 )-alkylsulfonyl, 
         and 
         where (C 2 -C 4 )-alkenyl and (C 2 -C 4 )-alkynyl may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         and 
         where (C 3 -C 7 )-cycloalkyl may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, chlorine, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         or 
         R 1  and R 2  together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle which may contain a further heteroatom from the group consisting of N, O and S, 
         where the 4- to 7-membered heterocycle may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, chlorine, oxo, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         R 11  represents hydrogen or the side group of a natural α-amino acid or its homologs or isomers, 
         R 12  represents hydrogen or methyl, 
         R 13A  represents hydrogen, (C 1 -C 4 )-alkyl, or an amino protective group, 
         R 14A  represents hydrogen or (C 1 -C 4 )-alkyl, or an amino protective group, 
         or 
         R 13A  and R 14A  together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycle, 
         where the 5- or 6-membered heterocycle may be substituted by 1 or 2 substituents independently selected from the group consisting of (C 1 -C 4 )-alkyl, amino, hydroxyl and (C 1 -C 4 )-alkoxy, 
         or 
         R 14A  together with R 11  and the atoms, to which they are attached, forms a pyrrolidine or piperidine ring, and 
         R 19  represents hydrogen or methyl, 
         or a salt thereof. 
       
     
     
         14 . A compound of formula (XVI): 
       
         
           
           
               
               
           
         
         L 1  represents (C 2 -C 6 )-alkanediyl, 
         L 2  represents (C 2 -C 6 )-alkanediyl, 
         R 1  represents hydrogen or (C 1 -C 4 )-alkyl, 
         R 2  represents (C 1 -C 6 )-alkyl, (C 2 -C 4 )-alkenyl, (C 2 -C 4 )-alkynyl or (C 3 -C 7 )-cycloalkyl, 
         where (C 1 -C 6 )-alkyl may be substituted by 1 to 3 substituents selected independently of one another from the group consisting of fluorine, chlorine, trifluoromethyl, trifluoromethoxy, (C 1 -C 4 )-alkoxy, (C 3 -C 7 )-cycloalkyl, (C 3 -C 7 )-cycloalkoxy, (C 1 -C 4 )-alkylsulfanyl and (C 1 -C 4 )-alkylsulfonyl, 
         and 
         where (C 2 -C 4 )-alkenyl and (C 2 -C 4 )-alkynyl may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         and 
         where (C 3 -C 7 )-cycloalkyl may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, chlorine, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         or 
         R 1  and R 2  together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycle which may contain a further heteroatom from the group consisting of N, O and S, 
         where the 4- to 7-membered heterocycle may be substituted by 1 or 2 substituents selected independently of one another from the group consisting of fluorine, chlorine, oxo, trifluoromethyl, (C 1 -C 4 )-alkyl, trifluoromethoxy and (C 1 -C 4 )-alkoxy, 
         R 15A  represents hydrogen, (C 1 -C 4 )-alkyl, or an amino protective group, 
         R 16A  represents hydrogen or (C 1 -C 4 )-alkyl, or an amino protective group, 
         or 
         R 15A  and R 16A  together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycle, 
         where the 5- or 6-membered heterocycle may be substituted by 1 or 2 substituents independently selected from the group consisting of (C 1 -C 4 )-alkyl, amino, hydroxyl and (C 1 -C 4 )-alkoxy, 
         R 19  represents hydrogen or methyl 
         or a salt thereof.