Chemical compounds and uses thereof
Disclosed herein are certain chemical compounds of Formula (I): that inhibit Werner Syndrome ATP dependent helicase enzyme (WRN) activity, in particular inhibit WRN helicase domain activity and are therefore useful in treating cancers treatable by inhibition of WRN, including cancers characterized by microsatellite instability (MSI) and/or defective DNA mismatch repair system (dMMR). Also, disclosed are pharmaceutical compositions comprising such compounds, methods of using such compounds, and methods making the same.
1 . A compound which is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
2 . A compound which is selected from the group consisting of
3 . A compound
or a pharmaceutically acceptable salt thereof.
4 . A compound
5 . A compound
or a pharmaceutically acceptable salt thereof.
6 . A compound
7 . A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof of claim 1 and a pharmaceutically acceptable excipient.
8 . A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof of claim 3 and a pharmaceutically acceptable excipient.
9 . A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof of claim 5 and a pharmaceutically acceptable excipient.
10 . A method of treatment of colorectal cancer in a human subject in need thereof comprising administering to said human subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof of claim 1 .
11 . A method of treatment of colorectal cancer in a human subject in need thereof comprising administering to said human subject a therapeutically effective amount of a pharmaceutical composition of claim 7 .
12 . A method of treatment of colorectal cancer in a human subject in need thereof comprising administering to said human subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof of claim 3 .
13 . A method of treatment of colorectal cancer of claim 10 , wherein the cancer is characterised by MSI-H and/or dMMR.
14 . A method of treatment of colorectal cancer of claim 12 , wherein the cancer is characterised by MSI-H and/or dMMR.