US 12,440,493 B2
Combination therapy for treating cancer comprising substituted piperazines
Nathan Arthur Brooks, Fishers, IN (US); and Raymond Gilmour, Indianapolis, IN (US)
Assigned to Eli Lilly and Company, Indianapolis, IN (US)
Appl. No. 17/912,383
Filed by Eli Lilly and Company, Indianapolis, IN (US)
PCT Filed Mar. 22, 2021, PCT No. PCT/US2021/023436
§ 371(c)(1), (2) Date Sep. 16, 2022,
PCT Pub. No. WO2021/194946, PCT Pub. Date Sep. 30, 2021.
Claims priority of provisional application 63/053,875, filed on Jul. 20, 2020.
Claims priority of provisional application 63/024,713, filed on May 14, 2020.
Claims priority of provisional application 62/993,254, filed on Mar. 23, 2020.
Prior Publication US 2023/0146387 A1, May 11, 2023
Int. Cl. C07D 241/08 (2006.01); A61K 31/496 (2006.01); A61K 31/519 (2006.01); A61K 31/553 (2006.01); A61K 31/706 (2006.01); A61K 31/7068 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01)
CPC A61K 31/519 (2013.01) [A61K 31/496 (2013.01); A61K 31/553 (2013.01); A61K 31/706 (2013.01); A61K 31/7068 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); A61P 35/02 (2018.01)] 27 Claims
 
1. A method for treating cancer in a human cancer subject having an isocitrate dehydrogenase (IDH) mutation, wherein the method comprises administering to the human cancer subject having an isocitrate dehydrogenase (IDH) mutation a therapeutically effective amount of:
(a) a first compound of the Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
R1 is CH2-cyclopropyl, CH2CH3, CH2CH2OCH3, or CH2CH(CH3)2;
R2 is CH3 or CH2CH3; and
X is CH or N; and
(b) at least one second compound selected from the group consisting of:
(i) an antimetabolite agent, or a pharmaceutically acceptable salt thereof;
(ii) a hypomethylating agent, or a pharmaceutically acceptable salt of thereof; and
(iii) a mutant Fms-like tyrosine kinase 3 (Flt3) inhibitor, or a pharmaceutically acceptable salt thereof,
or a combination thereof.