1,2,5-thiadiazolidin-3-one 1,1-dioxide containing compounds and uses thereof

A method of potentiating immunity of a subject in need thereof, comprising downregulating expression or activity of PTPN2 and/or PTP1B in a cell of the subject with a compound having the formula

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• R1 is selected from C2-6 alkyl and —C0-6 alkyl-(C3-8 carbocycle), each of which is optionally substituted with one, two, or three R20;
• R3 is selected from —C2 alkyl-(5- to 6-membered heterocycle) and —C(O)O—(C1-6 alkyl)-OR15, wherein-C2 alkyl-(5- to 6-membered heterocycle) is substituted with one, two, or three substituents independently selected from C1-3 alkyl and oxo;
• L1 is absent;
• R12 is independently selected at each occurrence from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle), wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle) are optionally substituted with one, two, or three R20;
• R13 is independently selected at each occurrence from hydrogen, C1-6 alkyl, and C1-6 haloalkyl;
• or R12 and R13 attached to the same nitrogen atom form 3- to 10-membered heterocycle optionally substituted with one, two, or three R20;
• R15 is selected at each occurrence from —C(O)R12 and —P(O)(X—R16)(Y—R17);
• X and Y are independently selected at each occurrence from —O— and —N(R12)—;
• R16 and R17 are independently selected at each occurrence from hydrogen, C1-6 alkyl, and phenyl, wherein C1-6 alkyl and phenyl are optionally substituted with one, two, or three substituents independently selected from halogen, —NO2, —CN, C3-12 carbocycle, 3- to 12-membered heterocycle, —OR12, —SR12, —N(R12)(R13), —C(O) OR12, —OC(O)N(R12)(R13), —N(R12)C(O)N(R12)(R13), —N(R12)C(O) OR12, —N(R12)S(O)2R12, —N(R12)S(O)2N(R12)(R13), —S—S—R12, —S—C(O)R12, —C(O)R12, —S(O)R12, —OC(O)R12, —OC(O)OR12, —C(O)N(R12)(R13), —C(O)C(O)N(R12)(R13), —N(R12)C(O)R12, —S(O)2R12, —S(O)(NR12)R12, —S(O)2N(R12)(R13), —S(O)(NR12)N(R12)(R13), —P(O)(OR12)2, —P(O)(R12)2, —OP(O)(OR12)2, ═O, ═S, and ═NR12;
• or R16 and R17 are taken together with the atoms to which they are attached to form 3- to 12-membered heterocycle optionally substituted with one, two, or three R20;
• R20 is independently selected at each occurrence from halogen, oxo, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, —C0-6 alkyl-(C3-12 carbocycle), -(2- to 6-membered heteroalkyl)-(C3-12 carbocycle), —C0-6 alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), —OR22, —SR22, —N(R22)(R23), ═NR22, ═C(R21)2, —C(O) OR22, —OC(O)N(R22)(R23), —N(R22)C(O)N(R22)(R23), —N(R22)C(O) OR22, —N(R22)S(O)2R22, —C(O)R22, —S(O)R22, —OC(O)R22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —N(R22)C(O)R22, —S(O)2R22, —S(O)(NR22)R22, —S(O)2N(R22)(R23)—, —S(═O)(═NR22)N(R22)(R23), and —OCH2C(O) OR22, wherein two R20 attached to the same or adjacent atoms optionally join to form C3-12 carbocycle or 3- to 12-membered heterocycle;
• wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, 2- to 6-membered heteroalkyl, 2- to 6-membered heteroalkenyl, 2- to 6-membered heteroalkynyl, —C0-6 alkyl-(C3-12 carbocycle), -(2- to 6-membered heteroalkyl)-(C3-12 carbocycle), —C0-6 alkyl-(3- to 12-membered heterocycle), -(2- to 6-membered heteroalkyl)-(3- to 12-membered heterocycle), C3-12 carbocycle, and 3- to 12-membered heterocycle are optionally substituted with one or more substituents independently selected from halogen, oxo, —CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, —OR22, —SR22, —N(R22)(R23), ═NR22, ═C(R21)2, —C(O) OR22, —OC(O)N(R22)(R23), —N(R22)C(O)N(R22)(R23), —N(R22)C(O) OR22, —N(R22)S(O)2R22, —C(O)R22, —S(O)R22, —OC(O)R22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —N(R22)C(O)R22, —S(O)2R22, —S(O)(NR22)R22, —S(O)2N(R22)(R23), and —S(═O)(═NR22)N(R22)(R23);
• R21 is independently selected at each occurrence from hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle), or two R21 are taken together with the carbon atom to which they are attached to form C3-12 carbocycle or 3- to 12-membered heterocycle, each of which is optionally substituted with one, two, or three substituents independently selected from halogen, C1-3 alkyl, C1-3 haloalkyl, and —OH;
• R22 is independently selected at each occurrence from hydrogen, C1-6 alkyl, C1-6 haloalkyl, —C0-6 alkyl-(C3-12 carbocycle), and —C0-6 alkyl-(3- to 12-membered heterocycle);
• R23 is independently selected at each occurrence from hydrogen and C1-6 alkyl;
• or R22 and R23 attached to the same nitrogen atom form 3- to 10 membered heterocycle;
• and
• indicates a single or double bond such that all valences are satisfied.