Novel Compounds with Analgesic Effect

Abstract

Compounds of general formula (I) are disclosed and claimed in the present application, as well as their pharmaceutically acceptable salts, pharmaceutical compositions comprising the novel compounds and their use in therapy, in particular in the management of pain.

1 - 26 . (canceled) 
     
     
         27 . A compound of the general formula (I) 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is hydrogen, a branched or straight C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 3 -C 8 cycloalkyl, (C 1 -C 2 alkyl)-(C 3 -C 6 cycloalkyl), C 6 -C 10 aryl, heteroaryl, (C 1 -C 2  alkyl)-(C 6 -C 10  aryl), (C 1 -C 2  alkyl)heteroaryl, 
       
       
         
           
           
               
               
           
         
       
       wherein said heteroaryl has from 5 to 10 atoms selected from C, S, N and/or O and wherein said aryl and/or heteroaryl may optionally and independently be substituted by 1 or 2 substituents selected from hydrogen, CH 3 , —(CH 2 ) q CF 3 , halogen, —CONR 5 R 4 , —COOR 5 , —COR 5 , —(CH 2 ) q NR 5 R 4 , —(CH 2 ) q CH 3 , —(CH 2 ) q SOR 5 , —(CH 2 ) q SO 2 R 5 , —(CH 2 ) q SO 2 NR 5 R 4 , and —(CH 2 ) q OR 5 , wherein q is 0, 1 or 2;
 R 2  and R 3  is each and independently selected from hydrogen and C 1 -C 6 alkyl; 
 A is 
 
       
         
           
           
               
               
           
         
         Z 1  and Z 2  is each independently selected from hydrogen, CH 3 , —(CH 2 ) r CF 3 , halogen, —CONR 6 R 7 , —CO 2 R 6 , —COR 6 , —(CH 2 ) r NR 6 R 7 , —(CH 2 ) r CH 3 , —(CH 2 ) r SOR 6 , —(CH 2 ) r SO 2 R 6  and —(CH 2 ) r SO 2 NR 6 R 7 , wherein r is 0, 1, or 2; 
         B is phenyl or naphthyl, wherein the phenyl and naphthyl is optionally and independently substituted by 1 or 2 substituents selected from hydrogen, CH 3 , —(CH 2 ) t CF 3 , halogen, —(CH 2 ) t CONR 5 R 4 , —(CH 2 ) t NR 5 R 4 , —(CH 2 ) t COR 5 , —(CH 2 ) t COOR 5 , —OR 5 , —(CH 2 ) t SOR 5 , —(CH 2 ) t SO 2 R 5 , and —(CH 2 ) t SO 2 NR 5 R 4 , wherein t is 0, 1, 2 or 3; 
         R 4 , R 5 , R 6 , and R 7  is each independently selected from hydrogen, a branched or straight C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 3 -C 8 cycloalkyl, and (C 1 -C 2 alkyl)-(C 3 -C 6 cycloalkyl); 
         R 12  and R 13  is each independently selected from hydrogen, a branched or straight C 1 -C 6  alkyl, C 1 -C 6 alkenyl, C 3 -C 8 cycloalkyl, (C 1 -C 2 alkyl)-(C 3 -C 6 cycloalkyl), and O—C 1 -C 3 alkyl; and 
         R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , and R 24  is each independently selected from hydrogen, C 1 -C 6 alkyl, and C 1 -C 6 alkenyl; 
         as well as pharmaceutically acceptable salts thereof. 
       
     
     
         28 . A compound according to  claim 27 , wherein R 12  and R 13  is each independently selected from hydrogen, a branched or straight C 1 -C 6  alkyl, and O—C 1 -C 3 alkyl. 
     
     
         29 . A compound according to  claim 28 , wherein R 1  is hydrogen or (C 1 -C 2  alkyl)-(C 6 -C 10  aryl). 
     
     
         30 . A compound according to  claim 29 , wherein R 2  and R 3  are hydrogen. 
     
     
         31 . A compound according to  claim 30 , wherein B is phenyl optionally and independently substituted by 1 or 2 substituents selected from halogen. 
     
     
         32 . A compound according to  claim 31 , wherein Z 1  and Z 2  are hydrogen. 
     
     
         33 . A compound according to  claim 27 , wherein R 1  is hydrogen or (C 1 -C 2  alkyl)-(C 6 -C 10  aryl). 
     
     
         34 . A compound according to  claim 27 , wherein R 2  and R 3  are hydrogen. 
     
     
         35 . A compound according to  claim 27 , wherein B is phenyl optionally and independently substituted by 1 or 2 substituents selected from halo-gen. 
     
     
         36 . A compound according to  claim 27 , wherein Z 1  and Z 2  are hydrogen. 
     
     
         37 . A compound according to  claim 27 , wherein R 1  is hydrogen or (C 1 -C 2  alkyl)-(C 6 -C 10  aryl); R 2  and R 3  are hydrogen; B is phenyl optionally and independently substituted by 1 or 2 substituents selected from halogen; Z 1  and Z 2  are hydrogen; and R 12  and R 13  is each independently selected from hydrogen, a branched or straight C 1 -C 6  alkyl, and O—C 1 -C 3 alkyl. 
     
     
         38 . A compound according to  claim 37 , wherein B is substituted by 1 substituent selected from halogen. 
     
     
         39 . A compound according to  claim 38 , wherein B is substituted by fluoro. 
     
     
         40 . A compound according to  claim 27 , wherein R 1  is hydrogen or benzyl; R 2  and R 3  are hydrogen; B is 3-fluorophenyl; Z 1  and Z 2  are hydrogen; and R 12  and R 13  is each independently selected from hydrogen, methyl, ethyl, methoxy, ethoxy, and isopropoxy. 
     
     
         41 . A pharmaceutical composition comprising a compound according to  claim 27  and a pharmaceutically acceptable carrier. 
     
     
         42 . A method of treating a patient for pain, comprising administering a therapeutically effective amount of a pharmaceutical composition according to  claim 41 . 
     
     
         43 . A compound according to  claim 27 , wherein said compound is selected from 
       
         
           
           
               
               
           
         
       
     
     
         44 . A pharmaceutical composition comprising a compound according to  claim 43  and a pharmaceutically acceptable carrier. 
     
     
         45 . A method of treating a patient for pain, comprising administering a therapeutically effective amount of a compound according to  claim 43 . 
     
     
         46 . A method of treating a patient for pain, comprising administering a therapeutically effective amount of a compound according to  claim 27 .