Inhibitors of arginase and their therapeutic applications

A compound according to Formula II,

• wherein
• R6 is selected from the group consisting of 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, —S(O)2—(C1-C6)alkyl, (C3-C14)aryl-S(O)2—, (C3-C14)heterocycloalkyl-(C1-C6)alkylene-, and (C3-C14)heteroaryl-(C1-C6)alkylene-;
• R7 is selected from the group consisting of H, straight or branched (C1-C6)alkyl, (C3-C14)aryl(C1-C6)alkylene-, (C3-C14)heteroaryl-(C1-C6)alkylene-, (C3-C14)heterocycloalkyl-(C1-C6)alkylene- and (C1-C6)alkyl-C(O)—;
• X is selected from the group consisting of (C3-C14)-cycloalkylene and (C3-C14)heterocycloalkylene,
• Y is selected from the group consisting of H, (C1-C14)alkyl, —NR′R″, hydroxy(C1-C6)alkylene, (C3-C14)-cycloalkyl, (C3-C14)-cycloalkyl-(C1-C6)alkylene, (C3-C14)aryl, (C3-C14)aryl-(C1-C6)alkylene, (C3-C14)heterocycloalkyl, (C3-C14)heterocycloalkyl-(C1-C6)alkylene, (C3-C14)heteroaryl, (C3-C14)heteroaryl-(C1-C6)alkylene, (C3-C14)heteroaryl-(C3-C6)heterocycloalkylene-, (C3-C14)aryl-(C3-C14)heterocycloalkylene-, (C3-C14)-aryl-(C1-C6)alkyl-(C3-C14)heterocycloalkylene-, (C3-C14)heteroaryl-(C1-C6)alkyl-(C3-C14)heterocycloalkylene-, and (C3-C14)heterocycloalkyl-(C1-C6)alkyl-(C3-C14)heterocycloalkylene-;
• M is selected from the group consisting of a bond, —(C1-C6)alkylene-, —O—, —C(O)—, —C(S)—, —C(O)NH—, —C(S)NH—, —S—, —S(O)—, —S(O)2—, —NR′—, and —C═NR11—;
• R8 and R9 are independently selected from hydrogen, straight or branched (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C14)aryl, and C(O)—R′,
• or R8 and R9 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 that optionally contains 1-3 additional heteroatom ring members selected from O, S, and N,
• wherein the ring is optionally fused with a cycloalkyl, heterocyclic or aromatic ring;
• D is selected from the group consisting of straight or branched (C3-C5)alkylene, straight or branched (C2-C8)alkenylene, straight or branched (C2-C8)alkynylene, (C3-C14)arylene, and (C3-C14)cycloalkylene,
• wherein one or more —CH2— groups in D are optionally and independently replaced with a moiety selected from group the consisting of O, NR′, S, SO, SO2, and CR′R″;
• or
• wherein any two adjacent —CH2— groups optionally represent two members of a (C3-C14)-cycloalkylenyl group;
• and
• wherein no two adjacent —CH2— groups are O, NR′, S, SO, or SO2;
• R′ and R″ are independently selected from the group consisting of H, (C1-C8)alkyl, —C(O)—(C1-C8)alkylene, optionally substituted (C3-C6)aryl, optionally substituted (C3-C14)aryl(C1-C6)alkylene-, optionally substituted (C1-C6)aminoalkyl, optionally substituted (C3-C6)cycloalkyl, optionally substituted (C3-C14)heterocycloalkyl, optionally substituted (C3-C14)heteroaryl;
• and
• wherein any alkyl, alkylene, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is optionally substituted with one or more members selected from the group consisting of halogen, oxo, —COOH, —CN, —NO2, —OH, —NRdRe, —NRgS(O)2Rh, (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)alkoxy, (C3-C14)aryl, (C3-C14)heteroaryl, (C3-C14)heterocycloalkyl, (C3-C14)heteroaryl-(C1-C6)alkylene and (C3-C14)aryloxy;
• wherein Rd, Re, Rg, and Rh are each independently selected from the group consisting of H, straight or branched (C1-C6)alkyl, optionally substituted (C3-C14)aryl(C1-C6)alkylene-, optionally substituted (C3-C14)aryl, (C1-C6)hydroxyalkyl, (C1-C6)aminoalkyl, H2N(C1-C6)alkylene-, optionally substituted (C3-C6)cycloalkyl, optionally substituted (C3-C14)heterocycloalkyl, optionally substituted (C3-C14)heteroaryl, optionally substituted (C3-C14)aryl-(C1-C6)alkylene-, and NR′R″C(O)—,
• or a pharmaceutically acceptable salt, stereoisomer, tautomer, or prodrug thereof.