Glutaminase inhibitors and method of use
Compounds and compositions comprising compounds that inhibit glutaminase are described herein. Also described herein are methods of using the compounds that inhibit glutaminase in the treatment of cancer.
1. A compound of formula (III) or a pharmaceutically acceptable salt thereof, wherein:
X is —SO 2 —;
each R 4 is independently aralkyl, heteroaralkyl, or heterocyclylalkyl, each of which is substituted with 0-3 occurrences of R 5 , or two adjacent R 5 moieties, taken together with the atoms to which they are attached form a heterocyclyl, heteroaryl, cycloalkyl or aryl;
each R 5 is independently oxo (═O), C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, cyano, halo, —OH, —SH, —OCF 3 , —SO 2 —C 1-6 alkyl, —NO 2 , —N(R 7 )—C(O)—C 1-6 alkyl, —N(R 6 ) 2 , —O—C(O)—C 1-6 alkyl, C 3-7 cycloalkyl, (C 3-7 cycloalkyl)alkyl, aryl, aryloxy, —C(O)-aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclylalkyl or heterocyclyl, wherein each aryl, heteroaryl or heterocyclyl is further substituted with 0-3 occurrences of R 7 ;
each R 6 is independently hydrogen, fluoro, OH or C 1-6 alkyl;
each R 7 is independently hydrogen, C 1-6 alkyl, —OH, —SH, cyano, halo, —CF 3 , —OCF 3 , —SO 2 —C 1-6 alkyl, —NO 2 , —N(R 7 )—C(O)—C 1-6 alkyl, —N(R 6 ) 2 or C 1-6 alkoxy;
m is 1, 2 or 3; and
n is 1, 2 or 3; provided that the sum of m and n is from 2 to 4.
2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein m and n are both 2.
3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:
4. A pharmaceutical composition comprising a compound of Formula (III) according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently aralkyl or heteroaralkyl, each of which is substituted with 0-3 occurrences of R 5 , or two adjacent R 5 moieties, taken together with the atoms to which they are attached form a heterocyclyl, heteroaryl, cycloalkyl or aryl.
6. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein each R 4 is heteroaralkyl.
7. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein each R 4 is aralkyl.
8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein each R 6 is hydrogen.