US 12,291,502 B2
Topoisomerase II-alpha inhibitors and methods of treating cancer using the same
Daniel V. LaBarbera, Aurora, CO (US); Qiong Zhou, Aurora, CO (US); and Adedoyin D. Abraham, Aurora, CO (US)
Assigned to The Regents of the University of Colorado, A Body Corporate, Denver, CO (US)
Appl. No. 17/599,193
Filed by The Regents of the University of Colorado, Denver, CO (US)
PCT Filed Apr. 1, 2020, PCT No. PCT/US2020/026206
§ 371(c)(1), (2) Date Sep. 28, 2021,
PCT Pub. No. WO2020/205991, PCT Pub. Date Oct. 8, 2020.
Claims priority of provisional application 62/827,818, filed on Apr. 1, 2019.
Prior Publication US 2023/0105776 A1, Apr. 6, 2023
Int. Cl. C07D 215/14 (2006.01); C07D 401/12 (2006.01); C07D 405/04 (2006.01)
CPC C07D 215/14 (2013.01) [C07D 401/12 (2013.01); C07D 405/04 (2013.01)] 19 Claims
 
1. A compound of formula:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, or solvate, thereof,
wherein:
R1 is —NR7CO—R8 or —CO—NR7—R8, wherein R7 is H or C1-C3 alkyl optionally substituted with one or more halogen, hydroxyl, or C1-C3 alkoxy and R8 is H, or alkyl, or cycloalkyl both optionally substituted with one or more halogen, hydroxyl, C1-C3 alkyl, C1-C3 alkoxy, or heterocyclic optionally substituted with one or more oxo (═O), halogen, hydroxyl, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 acyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 hydroxyalkyl, or heterocyclic;
R2, R3 and R5 are independently H, halogen, C1-C3 alkyl or OR9, wherein R9 is H or C1-C3 alkyl, where the C1-C3 alkyls are optionally substituted with one or more halogen, hydroxyl, C1-C3 alkoxy or C1-C3 hydroxyalkyl;
R4 is aryl or heteroaryl, which are optionally substituted with one or more halogen, hydroxyl, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 acyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 hydroxyalkyl, or heterocyclic; and
R6 is H, —COOR11, or —CONR12R13, wherein R11, R12, and R13 are independently alkyl or cycloalkyl each optionally substituted with one or more halogen, hydroxyl, C1-C3 alkyl, C1-C3 alkoxy, or heterocyclic which in turn is optionally substituted with one or more halogen, hydroxyl, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 acyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 hydroxyalkyl, or heterocyclic, or aryl or heterocyclic optionally substituted with one or more halogen, hydroxyl, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 acyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 hydroxyalkyl, or heterocyclic.