US 10,889,585 B2
Inhibitors of kidney-type glutaminase, GLS-1
Richard Cerione, Ithaca, NY (US); Kristin Cerione, Ithaca, NY (US); Clint Stalnecker, Ithaca, NY (US); and Scott Ulrich, Brooktondale, NY (US)
Assigned to CORNELL UNIVERSITY, Ithaca, NY (US); and ITHACA COLLEGE, Ithaca, NY (US)
Filed by CORNELL UNIVERSITY, Ithaca, NY (US); and ITHACA COLLEGE, Ithaca, NY (US)
Filed on Jan. 6, 2020, as Appl. No. 16/735,479.
Application 16/735,479 is a continuation of application No. 15/533,198, granted, now 10,526,322, previously published as PCT/US2015/064152, filed on Dec. 5, 2015.
Claims priority of provisional application 62/088,370, filed on Dec. 5, 2014.
Claims priority of provisional application 62/102,163, filed on Jan. 12, 2015.
Prior Publication US 2020/0216448 A1, Jul. 9, 2020
Int. Cl. C07C 211/52 (2006.01); C07C 211/58 (2006.01); C07C 211/59 (2006.01); C07C 217/90 (2006.01); C07C 237/40 (2006.01); C07C 311/21 (2006.01); C07D 207/16 (2006.01); C07D 221/04 (2006.01); C07D 221/06 (2006.01); C07D 221/12 (2006.01); C07D 221/18 (2006.01); C07D 233/61 (2006.01); C07D 277/82 (2006.01); C07D 295/135 (2006.01); C07D 401/10 (2006.01); C12N 9/80 (2006.01); C12N 9/96 (2006.01); C12Q 1/34 (2006.01); C07D 471/04 (2006.01); C07C 311/37 (2006.01); C07C 211/49 (2006.01)
CPC C07D 471/04 (2013.01) [C07C 211/49 (2013.01); C07C 211/52 (2013.01); C07C 211/58 (2013.01); C07C 211/59 (2013.01); C07C 217/90 (2013.01); C07C 237/40 (2013.01); C07C 311/21 (2013.01); C07C 311/37 (2013.01); C07D 207/16 (2013.01); C07D 221/04 (2013.01); C07D 221/06 (2013.01); C07D 221/12 (2013.01); C07D 221/18 (2013.01); C07D 233/61 (2013.01); C07D 277/82 (2013.01); C07D 295/135 (2013.01); C07D 401/10 (2013.01); C12N 9/80 (2013.01); C12N 9/96 (2013.01); C12Q 1/34 (2013.01); C12Y 305/01002 (2013.01); G01N 2333/98 (2013.01)] 19 Claims
 
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:
a compound of Formula IIA:

OG Complex Work Unit Drawing
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-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;
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, R11a, R13a, R14a, R15a, R16a, R17a, R18a, and R19a 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-R19a 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.