Inhibitors of creatine transport and uses thereof
This invention relates to compounds that inhibit creatine transport and/or creatine kinase, pharmaceutical compositions including such compounds, and methods of utilizing such compounds and compositions for the treatment of cancer.
1. A compound having the structure:
wherein Q1 is
m is 1 or 2;
R7 is hydrogen;
one R8 combines with R12 with the atoms to which they are attached to form an optionally substituted C3-C4 heterocycle;
a second R8, if present, is hydrogen, deuterium, halo, NH2, optionally substituted C1-C3 alkyl, or combines with an R9 and with the atoms to which they are attached to form an optionally substituted C3-C6 cycloalkyl ring; or combines with R10 or R11 and with the atoms to which they are attached to form an optionally substituted C3-C4 cycloalkyl ring;
each R9 is independently hydrogen, deuterium, halo, NH2, optionally substituted C1-C3 alkyl or combines with the second R8, if present, and with the atoms to which they are attached to form an optionally substituted C3-C6 cycloalkyl ring; or combines with R10 or R11 and with the atoms to which they are attached to form an optionally substituted C3-C4 cycloalkyl ring;
R10 and R11 are independently hydrogen, deuterium, optionally substituted C1-C4 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl or R10 and R11 combine with the atoms to which they are attached to form an optionally substituted C3-C6 cycloalkyl ring; or R10 or R11 combine with R8 or R9 with the atoms to which they are attached to form an optionally substituted C3-C4 cycloalkyl ring; or R10 or R11 combine with R12 with the atoms to which they are attached to form an optionally substituted C3-C4 heterocycle;
R12 is hydrogen, optionally substituted C1-C6 alkyl, or R12 combines with R8 or R9 with the atoms to which they are attached to form an optionally substituted C3-C4 heterocycle, or R12 combines with R10 or R11 with the atoms to which they are attached to form an optionally substituted C3-C4 heterocycle;
wherein if m is 1 and R10 is methyl then at least one of R9, and R11 is not hydrogen;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 10 is optionally substituted C 1 -C 4 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl.
3. The compound of claim 2 , wherein R 10 is methyl, ethyl, n-propyl, iso-propyl, —CD 3 , —CF 3 , —CH 2 F, —CHF 2 , —CH═CH 2 , or —C≡CH.
4. The compound of claim 2 , wherein R 11 is hydrogen or methyl.
5. The compound of claim 2 , wherein m is 2 and the second R 8 is hydrogen.
6. The compound of claim 2 , wherein R 9 is hydrogen, NH 2 , or methyl.
7. The compound of claim 1 , wherein said optionally substituted C3-C4 heterocycle is an optionally substituted C4 heterocycle.
8. A compound having the structure of Formula VIII:
wherein b is 0 or 1 and c is 0;
Q1 is
R9 is hydrogen, deuterium, halo, NH2, optionally substituted C1-C3 alkyl; and
R10 and R11 are, independently, hydrogen, deuterium, optionally substituted C1-C4 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, or a pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , wherein R10 is hydrogen or optionally substituted C1-C4 alkyl.
10. The compound of claim 9 , wherein R10 is hydrogen or methyl.
11. The compound of claim 1 , wherein R11 is hydrogen.
12. The compound of claim 1 , wherein R9 is hydrogen, halo, hydroxyl, NH2, optionally substituted C1-C3 alkyl.
13. The compound of claim 12 , wherein R9 is hydrogen, fluoro, hydroxyl, NH2, or methyl.
14. A compound having the structure:
or a pharmaceutically acceptable salt thereof.
15. A compound having the structure:
or a pharmaceutically acceptable salt thereof.
16. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.