Inhibitors of kidney-type glutaminase, gls-1

A compound, or a pharmaceutically acceptable salt, ester, enol ether, enol ester, solvate, hydrate, or prodrug thereof, wherein the compound is selected from the group consisting of:

• (i) a compound of Formula I:
• wherein:
• R is selected from the group consisting of monocyclic or bicyclic aryl, monocyclic or bicyclic heteroaryl, and monocyclic or bicyclic heterocyclyl, wherein each monocyclic or bicyclic aryl, monocyclic or bicyclic heteroaryl, and monocyclic or bicyclic heterocyclyl can be optionally substituted from 1 to 4 times with substituents independently selected at each occurrence thereof from the group consisting of H, halogen, C1-6 alkyl, aryl, —OR8, —CF3, and —CHF2;
• R1 and R2 are each independently selected from the group consisting of H, halogen, and C1-6 alkyl;
• or R1 and R2 are combined to form ═O;
• R3—R7 are each independently selected from the group consisting of H, halogen, —NO2, —NR8R9, —SO2NR8R9, —N3, —C(O)R8, aryl, heteroaryl, heterocyclyl,
• and
• R8 and R9 are each independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and aryl;
• or R8 and R9 are combined with the nitrogen to which they are attached to form a heterocyclyl, wherein the heterocyclyl can be optionally substituted with —COOH or —COOMe;
• (ii) a compound of Formula II:
• wherein:
• the dotted circle identifies an active moiety;
• X is independently —CR14a— or —N;
• R1a is independently H, —OH, —OR14a, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, R14aC(O)—, R14aOC(O)—, R14aS(O)—, or R14aS(O)2—;
• R2a, R3a, R4a, R5a, and R6a are each independently a photoreactive moiety, H, halogen, —NO2, —OH, —OR14a, —SR14a, —NH2, —NHR14a, —NR14aR15a, R14aC(O)—, R14aOC(O), R14aC(O)O—, C1-C6 alkyl, C2-6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl C1-C6 alkyl, mono or polycyclic aryl, or mono or polycyclic heteroaryl with each cyclic unit containing from 1 to 5 heteroatoms selected from the group consisting of nitrogen, sulfur, and oxygen, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, mono or polycyclic aryl, and mono or polycyclic heteroaryl are optionally substituted with a photoreactive moiety;
• or R2a and R3a, R3a and R4a, R4a and R5a, or R5a and R6a are combined to form a heterocyclic ring optionally substituted with a photoreactive moiety;
• R7a, R8a, R9a, and R10a are each independently a photoreactive moiety, H, —OH, —NH2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl C1-C6 alkyl, mono or polycyclic aryl, or mono or polycyclic heteroaryl with each cyclic unit containing from 1 to 5 heteroatoms selected from the group consisting of nitrogen, sulfur, and oxygen, wherein the aryl, heteroaryl, and aryl C1-C6 alkyl are optionally substituted from 1 to 3 times with substituents selected from the group consisting of, halogen, —OH, —NH2, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, —SH, and C1-C6 thioalkyl, and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, mono or polycyclic aryl, and mono or polycyclic heteroaryl are optionally substituted with a photoreactive moiety;
• and
• R11a, R12a, R13a, R14a, R15a, R16a, and R17a are each independently a photoreactive moiety, H, halogen, —OH, —NO2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl C1-C6 alkyl, mono or polycyclic aryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, and mono or polycyclic aryl are optionally substituted with a photoreactive moiety and each one of R11a-R17a is optionally substituted with —NH2, —OH, halogen, —COOH, —NO2, and —CN;
• and
• wherein the compound comprises at least one photoreactive moiety;
• and
• (iii) a compound of Formula III:
• wherein:
• R is selected from the group consisting of monocyclic or bicyclic aryl, monocyclic or bicyclic heteroaryl, and monocyclic or bicyclic heterocyclyl, wherein each monocyclic or bicyclic aryl, monocyclic or bicyclic heteroaryl, and monocyclic or bicyclic heterocyclyl can be optionally substituted from 1 to 4 times with substituents independently selected at each occurrence thereof from the group consisting of H, halogen, C1-6 alkyl, aryl, —OR8, —CF3, and —CHF2;
• R1 and R2 are each independently selected from the group consisting of a photoreactive moiety, H, halogen, and C1-6 alkyl optionally substituted with a photoreactive moiety;
• or R1 and R2 are combined to form ═O;
• R3—R7 are each independently selected from the group consisting of a photoreactive moiety, H, halogen, —NO2, —NR8R9, —SO2NR8R9, —N3, —C(O)R8, aryl, heteroaryl, and heterocyclyl, wherein the aryl and heteroaryl are optionally substituted with a photoreactive moiety;
• and
• R8 and R9 are each independently selected from the group consisting of a photoreactive moiety, H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and aryl, wherein the alkyl, alkenyl, alkynyl, and aryl are optionally substituted with a photoreactive moiety;
• or R8 and R9 are combined with the nitrogen to which they are attached to form a heterocyclyl, wherein the heterocyclyl can be optionally substituted with a photoreactive moiety, —COOH, or —COOMe;
• and
• wherein the compound comprises at least one photoreactive moiety;
• and
• wherein the compound is optionally modified to include a tag and/or an attachment to a solid surface.