Small molecule inhibitors of ubiquitin specific protease 1 (USP1) and uses thereof
The disclosure provides for small molecules inhibitory compounds of ubiquitin specific protease 1 (USP1) and compositions comprising the same. The disclosure further provides methods for targeting ubiquitin specific protease 1 (USP1) and methods of treating diseases or disorders related to USP1, such as cancer.
1 . A compound having the structure of Formula (VI), or a pharmaceutically acceptable salt thereof,
wherein:
ring A is pyridine or pyrimidine;
each R A is independently selected from CN, C 1-6 alkyl, C 3-8 cycloalkyl, and —OR 11 , wherein the C 3-8 cycloalkyl is substituted with one or more substituents independently selected from halogen, C 1-6 alkyl, C 1-6 alkoxyl, C 1-6 haloalkyl, oxo, C 3-6 cycloalkyl, and amino;
R 11 is hydrogen or C 1-6 alkyl;
R B is optionally substituted 5-membered monocyclic heteroaryl;
m is 1, 2, 3, or 4; and
p is 0 or 1.
2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein subscript p is 0.
3 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein subscript m is 1, 2, or 3.
4 . The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein ring A is pyridine.
5 . The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein ring A is pyrimidine.
6 . The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein
7 . The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein at least one R A is —OR 11 or C 3-8 cycloalkyl.
8 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R B is imidazole, pyrazole, triazole, or tetrazole, each of which is optionally substituted with one or more substituents selected from C 1-3 alkyl and C 1-3 haloalkyl.
9 . A compound which is
or a pharmaceutically acceptable salt thereof.
10 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.
11 . A pharmaceutical composition comprising a compound of claim 9 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.