Thieno[2,3-c] isoquinolines for use as inhibitors of parp

Abstract

The present invention relates to compounds for the inhibition of poly(ADP-ribose) polymerase (PARP). In some embodiments, the compounds have the Formula: wherein the constituent variables are as defined herein. The invention further provides methods for the use of the compounds disclosed herein.

1 .- 59 . (canceled) 
     
     
         60 . A compound of formula I, 
       
         
           
           
               
               
           
         
         wherein Y is a hetero atom selected from sulphur and nitrogen, 
         each of R 1 , R 2 , R 3 , R 4 , R 5  and R 6 , independently, is hydrogen, hydroxy, OR 7 , carboxy, COOR 7 , amino, NHR 7  or halogen, or R 5  and R 6  taken together form a fused aromatic 5-membered ring or a fused aromatic 6-membered heterocyclic ring, and 
         R 7  is C 1 -C 6  alkyl, C 2 -C 6  alkenyl or C 3 -C 7  cycloalkyl optionally substituted with one or more groups selected from hydroxy, C 1 -C 4  alkoxy, carboxy, C 1 -C 6  alkoxycarbonyl, amino, C 1 -C 6  mono-alkylamino, C 1 -C 6  di-alkylamino and halogen; 
         or a salt, solvate, or physiologically equivalent derivative thereof. 
       
     
     
         61 . The compound of  claim 60 , wherein Y is sulphur. 
     
     
         62 . The compound of  claim 60 , wherein Y is nitrogen. 
     
     
         63 . The compound of  claim 60 , wherein R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are each hydrogen. 
     
     
         64 . The compound of  claim 60 , wherein one of R 1 , R 2 , R 3 , R 4 , R 5  and R 6  is hydroxyl, OR 7 , COOR 7 , amino, NHR 7 , or halogen, and the others are each hydrogen. 
     
     
         65 . The compound of  claim 60 , wherein R 4  is hydrogen, hydroxy, OR 7 , or amino, and R 1 , R 2 , R 3 , R 5  and R 6  are each hydrogen. 
     
     
         66 . The compound of  claim 60 , wherein R 5  and R 6  taken together form a fused aromatic 5-membered ring. 
     
     
         67 . The compound of  claim 60 , wherein R 5  and R 6  taken together form a fused aromatic 6-membered heterocyclic ring. 
     
     
         68 . A pharmaceutical composition comprising a compound of  claim 60 , and a pharmaceutically acceptable vehicle. 
     
     
         69 . A method for treating an animal or human who has a condition selected from the group consisting of tumor disease, leukemia and sarcoma, who has a tissue damage due to ischemia or reperfusion, or who has an inflammatory disease, retinal ischemia, or cerebral trauma, the method comprising administering an effective quantity of a compound of Formula I to an animal or human, 
       
         
           
           
               
               
           
         
         wherein Y is a hetero atom selected from oxygen, sulphur, and nitrogen, 
         each of R 1 , R 2 , R 3 , R 4 , R 5  and R 6 , independently, is hydrogen, hydroxy, OR 7 , carboxy, COOR 7 , amino, NHR 7  or halogen, or R 5  and R 6  taken together form a fused aromatic or non-aromatic 5- or 6-membered ring, and 
         R 7  is C 1 -C 6  alkyl, C 2 -C 6  alkenyl or C 3 -C 7  cycloalkyl optionally substituted with one or more groups selected from hydroxy, C 1 -C 4  alkoxy, carboxy, C 1 -C 6  alkoxycarbonyl, amino, C 1 -C 6  mono-alkylamino, C 1 -C 6  di-alkylamino and halogen; 
         or a salt, solvate, or physiologically equivalent derivative thereof. 
       
     
     
         70 . The method of  claim 69 , wherein Y is sulphur. 
     
     
         71 . The method of  claim 69 , wherein Y is nitrogen. 
     
     
         72 . The method of  claim 69 , wherein R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are each hydrogen. 
     
     
         73 . The method of  claim 69 , wherein one of R 1 , R 2 , R 3 , R 4 , R 5  and R 6  is hydroxyl, OR 7 , COOR 7 , amino, NHR 7 , or halogen, and the others are each hydrogen. 
     
     
         74 . The method of  claim 69 , wherein R 4  is hydrogen, hydroxy, OR 7 , or amino, and R 1 , R 2 , R 3 , R 5  and R 6  are each hydrogen. 
     
     
         75 . The method of  claim 69 , wherein R 5  and R 6  taken together form a fused aromatic 5-membered ring. 
     
     
         76 . The method of  claim 69 , wherein R 5  and R 6  taken together form a fused aromatic 6-membered heterocyclic ring. 
     
     
         77 . The method of  claim 69 , wherein the compound of Formula I is administered in combination with ionizing agents or chemotherapeutic agents. 
     
     
         78 . The method of  claim 77 , wherein the animal or human has a condition selected from the group consisting of tumor disease, leukemia and sarcoma. 
     
     
         79 . The method of  claim 69 , wherein the animal or human has a tissue damage due to ischemia or reperfusion, or has an inflammatory disease, retinal ischemia, or cerebral trauma.