Arginase inhibitors as therapeutics

A compound having the structure of the formula:

• wherein
• R1 is selected from the group consisting of —OH, —ORa, and —NRbRc;
• Ra is selected from the group consisting of hydrogen, straight or branched chain (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C14)aryl, (C3-C14)heterocycloalkyl-(C1-C6)alkylene-, (C3-C14)heteroaryl-(C1-C6)alkylene-, and (C3-C14)aryl(C1-C6)alkylene-;
• Rb and Rc are each independently selected from the group consisting of H, —OH, straight or branched (C1-C6)alkyl, —SO2—(C1-C6)alkyl, (C3-C14)aryl-SO2—, (C3-C14)heterocycloalkyl-(C1-C6)alkylene-, and (C3-C14)heteroaryl-(C1-C6)alkylene-;
• R2 is selected from the group consisting of —NH2, —N3, —NH[straight or branched (C1-C6) alkyl], and —NHCO[(C1-C6)alkyl];
• R′″ is selected from H, —OH, —S(O)Rd, —S(O)2Rd, (C1-C8)alkyl, (C3-C14)aryl, —NH2, —NH(C1-C6)alkyl, —N[(C1-C6)alkyl]2, —C(O)NRdRe, —C(O)(C1-C6)alkyl, —C(O)(C3-C14)aryl, —C(O)O(C1-C6)alkyl, —C(O)O(C3-C14)aryl, (C3-C6)cycloalkyl, (C3—C14)heterocycloalkyl, —C(O)(C3-C14)heterocycloalkyl, (C3-C14)heteroaryl, (C3-C14)aryl-(C1-C6)alkylene-, —C(O)(C3-C14)aryl-(C1-C6)alkylene, (C3-C6)cycloalkyl-(C1-C6)alkylene-, (C3-C14)heteroaryl-(C1-C6)alkylene-, and (C3-C14)heterocycle-(C1-C6)alkylene-;
• R″″ is selected from H or
• R3 and R4 are each independently selected from straight or branched (C1-C6)alkyl and C(O)—R5, wherein R5 is selected from (C1-C8)alkyl, (C3-C14)aryl, —NH(C1-C6)alkyl, —N[(C1-C6)alkyl]2, (C3-C6)cycloalkyl, (C3-C14)heterocycloalkyl, (C3-C14)heteroaryl, (C3-C14)aryl-(C1-C6)alkylene-, (C3-C6)cycloalkyl-(C1-C6)alkylene-, (C3-C14)heteroaryl-(C1-C6)alkylene-, and (C3-C14)heterocycle-(C1-C6)alkylene-;
• or R3 and R4 together with the boron atom to which they are bound form a 5- or 6-membered ring that is fully saturated, or partially saturated;
• and
• is a single bond or double bond;
• wherein any alkyl, alkylene, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is optionally substituted with one or more members selected from halogen, oxo, —COOH, —CN, —NO2, —OH, —NRdRe, —NRgS(O)2Rh, (C1-C6)alkoxy, (C3-C14)aryl, (C1-C6)haloalkyl and (C3-C14)aryloxy;
• and
• wherein Rd, Re, Rg, and Rh are each independently selected from H, straight or branched (C1-C6)alkyl, (C3-C14)aryl-(C1-C6)alkylene-, (C3-C14)aryl, (C1-C6)hydroxyalkyl, (C1-C6)aminoalkyl, H2N(C1-C6)alkylene-, (C3-C6)cycloalkyl, (C3-C14)heterocycloalkyl, (C3-C14)heteroaryl, (C3-C14)aryl-(C1-C6)alkylene-, and (C3-C6)aryl-(C3-C14)-cycloalkylene-,
• or a pharmaceutically acceptable salt thereof.