Compounds, methods and pharmaceutical compositions for inhibiting parp

Abstract

The present invention provides compounds which inhibit poly(ADP-ribose) polymerase (“PARP”), compositions containing these compounds and methods for using these PARP inhibitors to treat, prevent and/or ameliorate the effects of the conditions described herein.

1 - 8 . (canceled) 
     
     
         9 . A method of radiosensitizing tumor cells in an animal comprising administering to said animal an effective amount of:
 a compound of formula (II), or a pharmaceutically acceptable salt, ester, solvate or hydrate thereof, wherein:   
       
         
           
           
               
               
           
         
       
       R1 is H, halogen or alkyl; 
       R2 is H, halogen or alkyl; 
       R3 is independently H, amino, hydroxy, —NH—NH2, halogen-substituted amino, —O-alkyl, —O-aryl, or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or —COR8, where R8 is H, —OH, an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, or —OR6 or —NR6R7 where R6 and R7 are each independently hydrogen or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; and 
       R4 is independently H, amino, hydroxy, —NH—NH 2 , —CO—NH—NH 2 , halogen-substituted amino, —O-alkyl, —O-aryl, or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —COR8, where R8 is H, —OH, an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or —CH 2 OH or —OR6 or —CH 2 NR6R7 or —CH 2 R6 or —NR6R7, where R6 and R7 are each independently hydrogen or an optionally-substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; or
 a compound selected from the group consisting of: 
 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         10 . The method of  claim 9 , wherein:
 R1 is H, F, Cl, methoxy, or methyl;   R2 is H, F, Cl, methoxy, or methyl; and   R3 is independently H, amino, hydroxy, —NH—NH2, halogen-substituted amino, —O-alkyl, —O-aryl, or an optionally substituted alkyl, alkenyl, —COR8, where R8 is H, —OH, an optionally substituted alkyl, alkenyl, alkynyl, or —OR6 or —NR6R7 where R6 and R7 are each independently hydrogen or an optionally substituted alkyl or alkenyl; and   R4 is independently H, amino, —NH—NH 2 , —CO—NH—NH 2 , halogen-substituted amino, —O-alkyl, —O-aryl, or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —COR8, where R8 is H, —OH, an alkyl or alkenyl, or —CH 2 OH or —CH 2 R6 or —OR6 or —CH 2 NR6R7 or —NR6R7 where R6 and R7 are each independently hydrogen or an optionally substituted alkyl or alkenyl.   
     
     
         11 . The method of  claim 10 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 9 , wherein the cancer cells are selected from the group consisting of ACTH-producing tumors, acute lymphocytic leukemia, acute nonlymphocytic leukemia, cancer of the adrenal cortex, bladder cancer, brain cancer, breast cancer, cervical cancer, chronic lymphocytic leukemia, chronic myelocytic leukemia, colorectal cancer, cutaneous T-cell lymphoma, endometrial cancer, esophageal cancer, Ewing's sarcoma, gallbladder cancer, hairy cell leukemia, head and neck cancer, Hodgkin's lymphoma, Kaposi's sarcoma, kidney cancer, liver cancer, lung cancer (small and/or non-small cell), malignant peritoneal effusion, malignant pleural effusion, melanoma, mesothelioma, multiple myeloma, neuroblastoma, non-Hodgkin's lymphoma, osteosarcoma, ovarian cancer, ovary (germ cell) cancer, prostate cancer, pancreatic cancer, penile cancer, retinoblastoma, skin cancer, soft-tissue sarcoma, squamous cell carcinomas, stomach cancer, testicular cancer, thyroid cancer, trophoblastic neoplasms, uterine cancer, vaginal cancer, cancer of the vulva and Wilm's tumor. 
     
     
         13 . The method of  claim 9 , wherein said mammal is a human.