Modulators of 5′-nucleotidase, ecto and the use thereof

A compound having the formula:

• or a pharmaceutically acceptable salt thereof, wherein,
• each R1 is independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, and —C(R2R2)—O—C(O)—OR3, or two R1 groups are optionally combined to form a 5- to 7-membered ring;
• each R2 is independently selected from the group consisting of H and optionally substituted C1-C6alkyl;
• each R3 is independently selected from the group consisting of H, C1-C6 alkyl, and optionally substituted aryl;
• R5 is selected from the group consisting of H and optionally substituted C1-C6 alkyl;
• X is selected from the group consisting of O, CH2, and S;
• A is selected from the group consisting of:
• each of which is optionally substituted with from 1 to 5 R6 substituents, and wherein the subscript n is an integer from 0 to 3;
• Z is selected from the group consisting of CH2, CHR6, NR6, and O;
• each R6 is independently selected from the group consisting of H, CH3, OH, CN, F, optionally substituted C1-C6 alkyl, and OC(O)—C1-C6 alkyl;
• and optionally two R6 groups on adjacent ring vertices are joined together to form a 5- to 6-membered ring having at least one heteroatom as a ring vertex;
• and
• Het is selected from the group consisting of:
• wherein the wavy line indicates the point of attachment to the remainder of the compound, and wherein:
• Ra is selected from the group consisting of H, NH2, NHR7, NHC(O)R7, NR7R7, R7, OH, SR7, and OR7;
• Rb is selected from the group consisting of H, halogen, NH2, NHR7, NR7R7, R7, OH, and OR7;
• Rc is selected from the group consisting of H, halogen, haloalkyl, NH2, NHR7, NR7R7, R7, OH, OR7, SR7, SO2R7, —X1—NH2, —X1—NHR7, —X1—NR7R7, —X1—OH, —X1—OR7, —X1—SR7, and —X1—SO2R7;
• Re and Rf are independently selected from the group consisting of H, halogen, and optionally substituted C1-C6 alkyl;
• each X1 is C1-C4alkylene;
• and
• each R7 is independently selected from the group consisting of optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, optionally substituted C3-C7 cycloalkyl, optionally substituted C3-C7 cycloalkylC1-C4alkyl, optionally substituted 4-7 membered cycloheteroalkyl, optionally substituted 4-7 membered cycloheteroalkylC1-C4alkyl, optionally substituted aryl, optionally substituted arylC1-C4alkyl, optionally substituted arylC2-C4alkenyl, optionally substituted arylC2-C4alkynyl, optionally substituted heteroaryl, optionally substituted heteroarylC1-C4alkyl, optionally substituted heteroarylC1-C4alkenyl, optionally substituted heteroarylC2-C4alkynyl, and optionally, two R7 groups attached to a nitrogen atom are joined together to form a 4- to 7-membered heterocyclic ring, optionally fused to an aryl ring.