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 a compound of Formula IIA:

• wherein:
• the dotted circle identifies an active moiety;
• 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-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 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;
• wherein at least two of R2a, R3a, R4a, R5a, and R6a are not hydrogen;
• 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 is optionally modified to include a tag and/or an attachment to a solid surface.