Inhibitors of creatine transport and uses thereof

A method of slowing the spread of gastrointestinal cancer, comprising administering to a subject in need thereof, a compound having the structure:

• wherein Q1 is optionally substituted amidino;
• m is 1 or 2;
• R7 is hydrogen, optionally substituted C1-C6 alkyl, or optionally substituted C5-C10 aryl C1-C6 alkyl;
• R8 and R9 are independently hydrogen, deuterium, halo, hydroxyl, NH2, optionally substituted C1-C3 alkyl, or R8 and R9 combine with the atoms to which they are attached to form an optionally substituted C3-C6 cycloalkyl ring;
• or R8 or R9 combine with R10 or R11 with the atoms to which they are attached to form an optionally substituted C3-C4 cycloalkyl ring;
• or R8 or R9 combine with R12 with the atoms to which they are attached to form an optionally substituted C3-C5 heterocycle;
• 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, C1-C5 alkyl, or R12 combines with R8 or R9 with the atoms to which they are attached to form an optionally substituted C3-C5 heterocycle, or R12 combines with R10 or R11 with the atoms to which they are attached to form an optionally substituted C3-C4 heterocycle;
• or a pharmaceutically acceptable salt thereof,
• in an amount sufficient to slow the spread of said gastrointestinal cancer.

A method of treating metastatic gastrointestinal cancer in a subject in need thereof comprising:

• (a) providing a subject identified as expressing CKB and/or SLC6a8;
• and
• (b) administering to said subject an effective amount of a compound having the structure:
• wherein Q1 is optionally substituted amidino;
• m is 1 or 2;
• R7 is hydrogen, optionally substituted C1-C6 alkyl, or optionally substituted C6-C10 aryl C1-C6 alkyl;
• R8 and R9 are independently hydrogen, deuterium, halo, hydroxyl, NH2, optionally substituted C1-C3 alkyl, or R8 and R9 combine with the atoms to which they are attached to form an optionally substituted C3-C6 cycloalkyl ring;
• or R8 or R9 combine with R10 or R11 with the atoms to which they are attached to form an optionally substituted C3-C4 cycloalkyl ring;
• or R8 or R9 combine with R12 with the atoms to which they are attached to form an optionally substituted C3-C5 heterocycle;
• 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, C1-C6 alkyl, or R12 combines with R8 or R9 with the atoms to which they are attached to form an optionally substituted C3-C5 heterocycle, or R12 combines with R10 or R11 with the atoms to which they are attached to form an optionally substituted C3-C4 heterocycle;
• or a pharmaceutically acceptable salt thereof.

A method for treating metastatic gastrointestinal cancer in a subject in need thereof, comprising contacting creatine transport channel SLC6a8 with a compound having the structure:

• wherein Q1 is optionally substituted amidino;
• m is 1 or 2;
• R7 is hydrogen, optionally substituted C1-C6 alkyl, or optionally substituted C6-C10 aryl C1-C6 alkyl;
• R8 and R9 are independently hydrogen, deuterium, halo, hydroxyl, NH2, optionally substituted C1-C3 alkyl, or R8 and R9 combine with the atoms to which they are attached to form an optionally substituted C3-C6 cycloalkyl ring;
• or R8 or R9 combine with R10 or R11 with the atoms to which they are attached to form an optionally substituted C3-C4 cycloalkyl ring;
• or R8 or R9 combine with R12 with the atoms to which they are attached to form an optionally substituted C3-C5 heterocycle;
• 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, C1-C6 alkyl, or R12 combines with R8 or R9 with the atoms to which they are attached to form an optionally substituted C3-C5 heterocycle, or R12 combines with R10 or R11 with the atoms to which they are attached to form an optionally substituted C3-C4 heterocycle;
• or a pharmaceutically acceptable salt thereof,
• in an amount effective to suppress metastatic colonization of said gastrointestinal cancer.