Imidazo[4,5-c]quinolin-2-one Compounds and Their Use in Treating Cancer

Abstract

The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, where R 1 , R 2 , R 3 , R 4 and R 5 have any of the meanings defined herein. The specification also relates to the use of compounds of Formula (I) and salts thereof to treat or prevent ATM mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising substituted imidazo[4,5-c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; and intermediates useful in such manufacture.

1 - 15 . (canceled) 
     
     
         16 . A method for treating cancer in a warm-blooded animal in need of such treatment, which comprises administering to said warm-blooded animal a therapeutically effective amount of 7-Fluoro-1-isopropyl-3-methyl-8-[6-[3-(1-piperidyl)propoxy]-3-pyridyl]imidazo[4,5-c]quinolin-2-one, or a pharmaceutically acceptable salt thereof wherein the cancer is selected from the group consisting of colorectal cancer, glioblastoma, gastric cancer, ovarian cancer, diffuse large B-cell lymphoma, chronic lymphocytic leukaemia, acute myeloid leukaemia, head and neck squamous cell carcinoma, breast cancer, triple negative breast cancer, hepatocellular carcinoma, small cell lung cancer and non-small cell lung cancer. 
     
     
         17 . The method according to  claim 16 , where 7-Fluoro-1-isopropyl-3-methyl-8-[6-[3-(1-piperidyl)propoxy]-3-pyridyl]imidazo[4,5-c]quinolin-2-one or a pharmaceutically acceptable salt thereof is administered simultaneously, separately or sequentially with radiotherapy. 
     
     
         18 . The method according to  claim 17 , wherein the cancer is glioblastoma. 
     
     
         19 . The method according to  claim 17 , wherein the cancer is colorectal. 
     
     
         20 . The method according to  claim 17 , wherein the cancer is hepatocellular carcinoma. 
     
     
         21 . The method according to  claim 16 , where 7-Fluoro-1-isopropyl-3-methyl-8-[6-[3-(1-piperidyl)propoxy]-3-pyridyl]imidazo[4,5-c]quinolin-2-one or a pharmaceutically acceptable slat thereof is administered simultaneously, separately or sequentially with at least one additional anti-tumour substance selected from the group consisting of doxorubicin, irinotecan, topotecan, etoposide, mitomycin, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, carmustine, melphalan and bleomycin. 
     
     
         22 . The method according to  claim 16 , further comprising administering to said warm-blooded animal a therapeutically effective amount of at least one additional anti-tumour substance selected from the group consisting of cisplatin, oxaliplatin, carboplatin, valrubicin, idarubicin, doxorubicin, pirarubicin, irinotecan, topotecan, amrubicin, epirubicin, etoposide, mitomycin, bendamustine, chlorambucil, cyclophosphamide, ifosfamide, carmustine, melphalan, bleomycin, olaparib, MEDI4736, AZD1775 and AZD6738. 
     
     
         23 . The method according to  claim 22 , wherein the at least one additional anti-tumour substance is MEDI4736. 
     
     
         24 . The method according to  claim 23 , wherein the cancer is selected from colorectal cancer, glioblastoma, gastric cancer, head and neck squamous cell carcinoma, triple negative breast cancer, hepatocellular carcinoma, small cell lung cancer and non-small cell lung cancer.