US 9,809,588 B2
GLS1 inhibitors for treating disease
Maria Emilia Di Francesco, Houston, TX (US); Philip Jones, Houston, TX (US); Timothy Heffernan, Sugar Land, TX (US); Matthew M. Hamilton, Missouri City, TX (US); Zhijun Kang, Sugar Land, TX (US); Michael J. Soth, Sugar Land, TX (US); Jason P. Burke, Houston, TX (US); Kang Le, Sugar Land, TX (US); Christopher Lawrence Carroll, Houston, TX (US); Wylie S. Palmer, Houston, TX (US); Richard Lewis, Houston, TX (US); Timothy McAfoos, Houston, TX (US); Barbara Czako, Houston, TX (US); Gang Liu, Sugar Land, TX (US); Jay Theroff, Manvel, TX (US); Zachary Herrera, Houston, TX (US); and Anne Yau, Houston, TX (US)
Assigned to Board of Regents, The University of Texas System, Austin, TX (US)
Filed by Board of Regents, The University of Texas System, Austin, TX (US)
Filed on Jul. 2, 2015, as Appl. No. 14/791,186.
Claims priority of provisional application 62/020,539, filed on Jul. 3, 2014.
Prior Publication US 2016/0009704 A1, Jan. 14, 2016
Int. Cl. C07D 417/14 (2006.01); C07D 417/06 (2006.01); C07D 403/06 (2006.01); C07D 405/14 (2006.01); C07D 403/14 (2006.01); C07D 493/08 (2006.01); C07D 401/14 (2006.01); A61K 31/433 (2006.01); A61K 31/501 (2006.01); A61K 31/497 (2006.01); A61K 45/06 (2006.01); A61K 31/4439 (2006.01); A61K 31/454 (2006.01); A61K 31/4192 (2006.01); A61K 31/444 (2006.01)
CPC C07D 417/14 (2013.01) [A61K 31/4192 (2013.01); A61K 31/433 (2013.01); A61K 31/444 (2013.01); A61K 31/4439 (2013.01); A61K 31/454 (2013.01); A61K 31/497 (2013.01); A61K 31/501 (2013.01); A61K 45/06 (2013.01); C07D 401/14 (2013.01); C07D 403/06 (2013.01); C07D 403/14 (2013.01); C07D 405/14 (2013.01); C07D 417/06 (2013.01); C07D 493/08 (2013.01)] 27 Claims
 
1. A compound of structural Formula IV:

OG Complex Work Unit Drawing
or a salt thereof, wherein:
RX is chosen from fluoro and H;
R1 is chosen from alkenyl, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, H, halo, haloalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkylalkyl, wherein R1 may be optionally substituted with one to three RZ groups;
each R4 is independently chosen from alkenyl, alkoxy, alkyl, aryl, arylalkyl, cyano, cycloalkyl, cycloalkylalkyl, H, halo, haloalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, and hydroxyl, wherein R4 may be optionally substituted with one to three RZ groups;
each RZ group is independently chosen from alkenyl, alkoxy, alkoxyalkyl, alkoxyaryl, alkoxyarylalkyl, alkoxycycloalkyl, alkoxycycloalkylalkyl, alkoxyhaloalkyl, alkoxyheteroaryl, alkoxyheteroarylalkyl, alkoxyheterocycloalkyl, alkoxyheterocycloalkylalkyl, alkyl, alkylaryl, alkylarylalkyl, alkylcycloalkyl, alkylcycloalkylalkyl, alkylheteroaryl, alkylheteroarylalkyl, alkylheterocycloalkyl, alkylheterocycloalkylalkyl, aryl, arylalkyl, arylalkyloxy, arylhaloalkyl, aryloxy, cyano, cycloalkyl, cycloalkylalkyl, cycloalkylalkyloxy, cycloalkylhaloalkyl, cycloalkyloxy, H, halo, haloalkoxy, haloalkoxyalkyl, haloalkoxyaryl, haloalkoxyarylalkyl, haloalkoxycycloalkyl, haloalkoxycycloalkylalkyl, haloalkoxyheteroaryl, haloalkoxyheteroarylalkyl, haloalkoxyheterocycloalkyl, haloalkoxyheterocycloalkylalkyl, haloalkyl, haloalkylaryl, haloalkylarylalkyl, haloalkylcycloalkyl, haloalkylcycloalkylalkyl, haloalkylheteroaryl, haloalkylheteroarylalkyl, haloalkylheterocycloalkyl, haloalkylheterocycloalkylalkyl, haloaryl, haloarylalkyl, haloarylalkyloxy, haloaryloxy, halocycloalkyl, halocycloalkylalkyl, halocycloalkylalkyloxy, halocycloalkyloxy, haloheteroaryl, haloheteroarylalkyl, haloheteroarylalkyloxy, haloheteroaryloxy, haloheterocycloalkyl, haloheterocycloalkylalkyl, haloheterocycloalkylalkyloxy, haloheterocycloalkyloxy, heteroaryl, heteroarylalkyl, heteroarylalkyloxy, heteroarylhaloalkyl, heteroaryloxy, heterocycloalkyl, heterocycloalkylalkyl, heterocycloalkylalkyloxy, heterocycloalkylhaloalkyl, heterocycloalkyloxy, hydroxyl, oxo, N(R5)2, NR5C(O)R5, NR5C(O)OR5, NR5C(O)N(R5)2, NR5S(O)R5, NR5S(O)2R5, C(O)N(R5)2, S(O)N(R5)2, S(O)2N(R5)2, C(O)R5, C(O)OR5, SR5, S(O)R5, and S(O)2R5; and
each R5 is independently chosen from alkenyl, alkoxy, alkyl, aryl, arylalkyl, cyano, cycloalkyl, cycloalkylalkyl, H, haloalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, and heterocycloalkylalkyl, wherein two R5 groups together with the atoms to which they are attached optionally form an aryl, cycloalkyl, heteroaryl, or heterocycloalkyl ring, which may be optionally substituted with one to three RX groups.