Inhibitors of microbial beta-glucuronidase enzymes and uses thereof
Compounds and compositions are provided that comprise selective b-glucuronidase inhibitors. The compounds and compositions can ameliorate the side effects of chemotherapeutic agents and can improve the efficacy of such agents, including irinotecan and non-steroidal anti-inflammatory drugs.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof,
wherein,
R 1 is
wherein t and q are each 1, R 7 is H, and R 8 is H;
R 2 is —NR F R G , wherein;
R F and R G are independently selected from the group consisting of H, linear or branched C 1-6 alkyl optionally substituted with halo, amino or hydroxyl, optionally substituted benzyl, and C 3-8 cycloalkyl;
and
R 4 and R 5 are taken together with the carbon to which each is attached to form an optionally substituted cyclohexyl ring.
2. A compound having the structure
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , which is selected from