Chemical Compounds

Abstract

The present invention relates to imidazopyridazine derivatives. More particularly, it relates to 4-(biphenyl-3-yl)-7H-imidazo[4,5-c]pyridazine derivatives of formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the description. The imidazopyridazine derivatives of the present invention modulate the activity of the GABA A receptor. They are useful in the treatment of a number of conditions, including pain.

1 . A compound according to formula (I) 
       
         
           
           
               
               
           
         
         wherein
 R 1  is selected from (C 1 -C 4 )alkyl, (C 3 -C 4 )cycloalkyl, NH 2 , and NH(C 1 -C 4 )alkyl and R 2  is H; or 
 R 1  and R 2  together are —CH 2 —CH 2 — or —N(CH 3 )—CH 2 —; 
 R 3  is selected from H, F, CHF 2 , OCH 3  and CN; 
 R 4  is selected from H, F, Cl, OH, OCH 3  and CN; and 
 R 5  is selected from (C 2 -C 4 )alkyl, (C 3 -C 5 )cycloalkyl and methyl-substituted (C 3 -C 5 )cycloalkyl, 
 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The compound according to  claim 1  wherein R 1  is (C 2 -C 4 )alkyl and R 2  is H, or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The compound according to  claim 1  wherein R 3  is selected from F and OCH 3 , or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The compound according to  claim 1  wherein R 4  is selected from H and F, or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The compound according to  claim 1  wherein R 5  is (C 2 -C 4 )alkyl, or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The compound according to  claim 1  selected from:
 7-ethyl-4-(6-fluoro-4′-((1-methylethyl)sulfonyl)biphenyl-3-yl)-7H-imidazo[4,5-c]pyridazine; 
 4-(4′-ethanesulfonyl-6-fluoro-2′-methoxybiphenyl-3-yl)-7-ethyl-7H-imidazo[4,5-c]pyridazine; 
 7-cyclopropyl-4-(4′-ethylsulfonyl-6-fluorobiphenyl-3-yl)-7H-imidazo[4,5-c]pyridazine; and 
 4-(4′-ethanesulfonyl-2′,6-difluorobiphenyl-3-yl)-7-(1-methylethyl)-7H-imidazo[4,5-c]pyridazine. 
 
     
     
         7 . The compound 4-(4′-ethanesulfonyl-6-fluoro-2′-methoxybiphenyl-3-yl)-7-ethyl-7H-imidazo[4,5-c]pyridazine. 
     
     
         8 . The compound 4-(4′-ethanesulfonyl-6-fluoro-2′-methoxybiphenyl-3-yl)-7-ethyl-7H-imidazo[4,5-c]pyridazine or a pharmaceutically acceptable salt thereof. 
     
     
         9 . A pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         10 . A method of treating pain comprising the administration to a subject in need of such treatment of an effective amount of a compound according to  claim 1 . 
     
     
         11 . A combination comprising a compound according to  claim 1  and a second pharmaceutically active agent.