Substituted 5,6,7,8-Tetrahydro-pyrido[4,3-d]pyrimidine-2-yl Compounds and 5,6,7,8-Tetrahydro-quinazoline-2-yl Compounds

Abstract

Substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds, corresponding to formula I processes for the production thereof, pharmaceutical preparations containing these compounds the use thereof for the production of pharmaceutical preparations and related method of treating or inhibiting certain disorders or conditions, including pain.

1 . A process for preparing a substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl compound corresponding to formula I: 
     
       
         
         
             
             
         
       
       wherein 
       X represents an NR 2a  group; 
       R 1  represents a —C(═O)—R 3  group or a —C(═O)—O—R 4  group; 
       R 2a  represents a —C(═O)—R 5  group or an —S(═O) 2 —R 6  group; 
       R 3  represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
       R 4  represents an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
       R 5  represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link;
 an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; 
 an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene, alkenylene or alkynylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; 
 a —C(═O)—R 7  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
 a —C(═O)—R 8  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, or 
 an —N(H)—C(═O)—O—R 9  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one —N(H)—C(═O) or at least one —C(═O)—N(H) grouping as a chain link; 
 
       R 6  represents an —NR 10 R 11  group;
 a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; 
 an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, and which may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be bridged with a linear or branched alkylene group; or 
 an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group or may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system; 
 
       R 7  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, or an —NR 7a R 7b  group, wherein R 7a  and R 7b , identically or differently, in each case, represent a linear or branched alkyl group, 
       R 8  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached by a linear or branched alkylene group, 
       R 9  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched alkylene group, or an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may be fused with at least one unsubstituted or at least monosubstituted mono- or polycyclic ring system, 
       R 10  and R 11 , identically or differently, in each case, represent a linear or branched alkyl group, 
       or a salt thereof, 
       said process comprising: 
       reacting a protected piperidin-4-one corresponding to formula II, 
     
     
       
         
         
             
             
         
       
       wherein PG represents a protective group, with a dimethoxy-methyl-dimethyl-amine corresponding to formula III 
     
     
       
         
         
             
             
         
       
       in an organic reaction medium to yield a compound corresponding to formula IV, 
     
     
       
         
         
             
             
         
       
       and optionally purifying or isolating said compound corresponding to formula IV, and 
       reacting said compound corresponding to formula IV with guanidine corresponding to formula V, 
     
     
       
         
         
             
             
         
       
       which guanidine corresponding to formula V may be present in the form of a salt, in an organic reaction medium, which step of reacting may include the presence of at least one base, to yield a compound corresponding to formula VI, 
     
     
       
         
         
             
             
         
       
       and optionally purifying or isolating said compound corresponding to formula VI, and reacting said compound corresponding to formula VI in an organic reaction medium, which may optionally include at least one base or at least one catalyst, with a compound corresponding to the formula R 3 —C(═O)—X 1  or a compound corresponding to the formula (R 3 —C(═O)) 2 O, or 
       reacting said compound corresponding to formula VI with a compound corresponding to the formula R 3 —C(═O)—OH in an organic reaction medium in the presence of at least one coupling agent, which may include at least one base, or 
       reacting said compound corresponding to formula VI with a compound corresponding to formula R 4 —O—C(═O)—X 1a  in an organic reaction medium, which may include at least one base, 
       wherein X 1  and X 1a  in each case denote a leaving group, to yield a compound corresponding to formula VII, 
     
     
       
         
         
             
             
         
       
       and optionally purifying or isolating said compound corresponding to formula VII, and 
       eliminating the protective group PG to yield a compound corresponding to formula VIII, 
     
     
       
         
         
             
             
         
       
       or a salt thereof, and optionally purifying or isolating the compound corresponding to formula VIII or the salt thereof and reacting said compound corresponding to formula VIII or the salt thereof with a compound of corresponding to the formula R 5 —C(═O)—X 2  or (R 5 —C(═O)) 2 O, in an organic reaction medium, optionally including at least one base or at least one catalyst, or 
       reacting said compound corresponding to formula VIII or the salt thereof with a compound corresponding to the formula R 6 —SO 2 —X 3 , wherein X 3  represents a leaving group, in an organic reaction medium, optionally including at least one base, or 
       reacting said compound corresponding to formula VIII or the salt thereof with a compound corresponding to the formula R 5 —COOH, in an organic reaction medium, in the presence of at least one suitable coupling agent, optionally including at least one base, 
       to yield a compound corresponding to formula IX 
     
     
       
         
         
             
             
         
       
       and optionally purifying or isolating said compound corresponding to formula IX and optionally converting said compound corresponding to formula IX to yield a corresponding salt and optionally purifying or isolating the corresponding salt of said compound corresponding to formula IX, or 
       reacting a piperidin-4-one corresponding to formula X 
     
     
       
         
         
             
             
         
       
       or a salt thereof, with a compound corresponding to the formula R 5 —C(═O)—X 2  or (R 5 —C(═O)) 2 O, wherein X 2  represents a leaving group, in an organic reaction medium, which may include at least one base or at least one catalyst, or 
       with a compound of corresponding to the formula R 6 —SO 2 —X 3 , wherein X 3  represents a leaving group, in an organic reaction medium, which may include at least one base, or 
       with a compound corresponding to the formula R 5 —COOH, in the presence of a suitable coupling agent, and in an organic reaction medium, which may include at least one base, to yield a compound corresponding to formula XI, 
     
     
       
         
         
             
             
         
       
       and optionally purifying or isolating the compound corresponding to formula XI, and reacting said compound corresponding to formula XI with a dimethoxy-methyl-dimethyl-amine corresponding to formula III 
     
     
       
         
         
             
             
         
       
       in an organic reaction medium to form a compound corresponding to formula XII, 
     
     
       
         
         
             
             
         
       
       and optionally purifying or isolating said compound corresponding for formula XII, and reacting said said compound corresponding for formula XII with a guanidine corresponding to formula V, 
     
     
       
         
         
             
             
         
       
       or a salt thereof, in an organic reaction medium which may include at least one base, to yield a compound corresponding to formula XIII 
     
     
       
         
         
             
             
         
       
       and optionally purifying or isolating said compound corresponding to formula XIII and reacting said compound corresponding to formula XIII 
       in an organic reaction medium, which may include at least one base or at least one catalyst, with a compound corresponding to the formula R 3 —C(═O)) 2 O or with a compound corresponding to the formula R 3 —C(═O)—X 1 , or 
       with a compound corresponding to the formula R 3 —COOH, in an organic reaction medium which may include at least one base and in the presence of at least one coupling agent, or 
       with a compound corresponding to the formula R 4 —O—C(═O)—Xla in an organic reaction medium, which may include at least one base, 
       wherein X 1  and X 1a  in each case represent a leaving group, to yield a compound corresponding to formula XIV 
     
     
       
         
         
             
             
         
       
       and optionally purifying or isolating the compound corresponding to formula XIV and optionally converted compound corresponding to formula XIV to yield a corresponding salt and optionally purifying or isolating the salt of the compound corresponding to formula XIV. 
     
   
   
       2 . A method of noradrenalin receptor regulation, 5-HT receptor regulation, mGluR5 receptor regulation or batrachotoxin receptor regulation, said method comprising administering to a subject in need thereof a pharmaceutically effective amount of a compound corresponding to formula I: 
     
       
         
         
             
             
         
       
       wherein 
       X represents an NR 2a  group; 
       R 1  represents a —C(═O)—R 3  group or a —C(═O)—O—R 4  group; 
       R 2a  represents a —C(═O)—R 5  group or an —S(═O) 2 —R 6  group; 
       R 3  represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
       R 4  represents an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
       R 5  represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link;
 an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; 
 an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene, alkenylene or alkynylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; 
 a —C(═O)—R 7  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
 a —C(═O)—R 8  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, or 
 an —N(H)—C(═O)—O—R 9  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one —N(H)—C(═O) or at least one —C(═O)—N(H) grouping as a chain link; 
 
       R 6  represents an —NR 10 R 11  group;
 a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; 
 an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, and which may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be bridged with a linear or branched alkylene group; or 
 an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group or may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system; 
 
       R 7  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, or an —NR 7a R 7b  group, wherein R 7a  and R 7b , identically or differently, in each case, represent a linear or branched alkyl group, 
       R 8  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached by a linear or branched alkylene group, 
       R 9  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched alkylene group, or an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may be fused with at least one unsubstituted or at least monosubstituted mono- or polycyclic ring system, 
       R 10  and R 11 , identically or differently, in each case, represent a linear or branched alkyl group, 
       or a pharmaceutically acceptable salt thereof. 
     
   
   
       3 . The method of  claim 2 , wherein said method is effective for inhibiting noradrenalin reuptake or for inhibiting 5-hydroxy-tryptophan reuptake. 
   
   
       4 . A method of treating or inhibiting a condition mediated at least in part by at least one receptor selected from the group consisting of noradrenalin-receptors, 5-HT receptors, mGluR5 receptors and batrachotoxin receptors, said method comprising administering to a subject in need thereof a pharmaceutically effective amount of a compound corresponding to formula I: 
     
       
         
         
             
             
         
       
       wherein 
       X represents an NR 2a  group; 
       R 1  represents a —C(═O)—R 3  group or a —C(═O)—O—R 4  group; 
       R 2a  represents a —C(═O)—R 5  group or an —S(═O) 2 —R 6  group; 
       R 3  represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
       R 4  represents an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
       R 5  represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link;
 an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; 
 an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene, alkenylene or alkynylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; 
 a —C(═O)—R 7  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
 a —C(═O)—R 8  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, or 
 an —N(H)—C(═O)—O—R 9  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one —N(H)—C(═O) or at least one —C(═O)—N(H) grouping as a chain link; 
 
       R 6  represents an —NR 10 R 11  group;
 a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; 
 an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, and which may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be bridged with a linear or branched alkylene group; or 
 an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group or may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system; 
 
       R 7  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, or an —NR 7a R 7b  group, wherein R 7a  and R 7b , identically or differently, in each case, represent a linear or branched alkyl group, 
       R 8  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached by a linear or branched alkylene group, 
       R 9  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched alkylene group, or an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may be fused with at least one unsubstituted or at least monosubstituted mono- or polycyclic ring system, 
       R 10  and R 11 , identically or differently, in each case, represent a linear or branched alkyl group, 
       or a pharmaceutically acceptable salt thereof. 
     
   
   
       5 . A method according to  claim 4 , wherein said condition comprises pain in a mammal, said method comprising administering to said mammal an effective pain alleviating amount of said compound corresponding to formula I. 
   
   
       6 . A method according to  claim 4 , wherein said condition is selected from the group consisting of migraine, depression, urinary incontinence, coughing, neurodegenerative diseases, food intake disorders, cognitive dysfunction, cognitive deficiency states, disorders of the nervous system, epilepsy, schizophrenia, cerebral ischaemia, muscle spasms, cramps, diarrhea, pruritus, gastro-oesophageal reflux syndrome, panic attacks, alcohol or drug abuse or abuse of medicines, alcohol or drug dependency or dependency on medicines, withdrawal symptoms associated with alcohol or drug dependency or dependency on medicines, tolerance to medicines, locomotor activity disorders, irregularaties of the cardiovascular system, pain, anxiety, decreased vigilance, decreased libido, diuresis, and antinatriuresis, said method comprising administering to a subject in need thereof a pharmaceutically effective amount of said compound corresponding to formula I. 
   
   
       7 . A method according to  claim 6 , wherein said condition is a neurodegenerative disease selected from the group consisting of Parkinson's disease, Huntington's chorea, Alzheimer's disease and multiple sclerosis; or a food intake disorder selected from the group consisting of bulimia, anorexia, obesity and cachexia; or a cognitive memory disorder; or a tolerance opioids. 
   
   
       8 . A method of preparing a pharmaceutical formulation for noradrenalin receptor regulation, for 5-HT receptor regulation, for mGluR5 receptor regulation or for batrachotoxin receptor regulation comprising combining a pharmaceutically effective amount of a compound corresponding to formula I: 
     
       
         
         
             
             
         
       
       wherein 
       X represents an NR 2a  group; 
       R 1  represents a —C(═O)—R 3  group or a —C(═O)—O—R 4  group; 
       R 2a  represents a —C(═O)—R 5  group or an —S(═O) 2 —R 6  group; 
       R 3  represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
       R 4  represents an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
       R 5  represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link;
 an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; 
 an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene, alkenylene or alkynylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; 
 a —C(═O)—R 7  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; 
 a —C(═O)—R 8  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, or 
 an —N(H)—C(═O)—O—R 9  group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one —N(H)—C(═O) or at least one —C(═O)—N(H) grouping as a chain link; 
 
       R 6  represents an —NR 10 R 11  group;
 a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; 
 an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, and which may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be bridged with a linear or branched alkylene group; or 
 an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group or may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system; 
 
       R 7  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, or an —NR 7a R 7b  group, wherein R 7a  and R 7b , identically or differently, in each case, represent a linear or branched alkyl group, 
       R 8  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached by a linear or branched alkylene group, 
       R 9  represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched alkylene group, or an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may be fused with at least one unsubstituted or at least monosubstituted mono- or polycyclic ring system, 
       R 10  and R 11 , identically or differently, in each case, represent a linear or branched alkyl group, 
       or a pharmaceutically acceptable salt thereof, 
       with at least one physiologically acceptable auxiliary substance, and 
       forming the combined substances into a pharmaceutically administrable dosage form. 
     
   
   
       9 . A method according to  claim 8 , wherein said pharmaceutical formulation is effective for inhibiting noradrenalin reuptake or for inhibiting 5-hydroxy-tryptophan reuptake.