US 12,378,201 B2
Histone demethylase inhibitors for treating cancers
Jer-Tsong Hsieh, Plano, TX (US); Jung-Mo Ahn, Plano, TX (US); and Zhi-Ping Liu, Dallas, TX (US)
Assigned to Board of Regents, The University of Texas System, Austin, TX (US)
Appl. No. 17/596,816
Filed by The Board of Regents of the University of Texas System, Austin, TX (US)
PCT Filed Jun. 20, 2020, PCT No. PCT/US2020/038843
§ 371(c)(1), (2) Date Dec. 17, 2021,
PCT Pub. No. WO2020/257733, PCT Pub. Date Dec. 24, 2020.
Claims priority of provisional application 62/864,210, filed on Jun. 20, 2019.
Prior Publication US 2022/0306584 A1, Sep. 29, 2022
Int. Cl. C07D 215/26 (2006.01); A61P 35/00 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 405/14 (2006.01)
CPC C07D 215/26 (2013.01) [A61P 35/00 (2018.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 405/14 (2013.01)] 19 Claims
 
1. A histone demethylase inhibitor, or a pharmaceutically acceptable salt thereof, having a structure given by the formula:

OG Complex Work Unit Chemistry
where R1 is a group having a structure selected from the formulas:

OG Complex Work Unit Chemistry
where n is from 0 to 10;
where o is from 0 to 10;
where p is from 0 to 10;
where each of R11 and R12, when present, is independently selected from hydrogen, halogen, hydroxy, thiol, cyano, amino, nitro, C1-C10 alkylamide, carbonyl, carboxylic acid, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 heterocycloalkyl, aryl, heteroaryl, arylalkyl, and alkylaryl, and where each occurrence of C1-C10 alkylamide, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 heterocycloalkyl, aryl, heteroaryl, and arylalkyl, alkylaryl is optionally substituted with halogen, hydroxy, alkoxy, thiol, thioether, cyano, amino, carboxylic acid, ester, amide, carbamate, urea, guanidine, aryl substituted organic hydrazone, lactam substituted aryl group, nitro, —O—(C1-C6 alkyl), —NR40R41 C1-C6 alkylhydroxyl, C1-C6 haloalkyl, C1-C6 cycloalkyl, C1-C6 alkylamino, —OR40, —COR40, —CO2R40, aryl, and —CONR40R41;
where each of R20 and R21, when present, is selected from hydrogen, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 heterocycloalkyl, aryl, heteroaryl, C1-C20 alkylheteroaryl, arylalkyl, alkylaryl, —P(═O)(OH)R40R41, —SR40, —S(═O) 2R40R41, and —NR40R41 and where each occurrence of C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 heterocycloalkyl, aryl, heteroaryl, and arylalkyl, alkylaryl is optionally substituted with halogen, hydroxy, thiol, cyano, amino, carboxylic acid, ester, amide, carbamate, urea, guanidine, nitro, —O—(C1-C6 alkyl), —NR40R41, C1-C6 alkylhydroxyl, C1-C6 haloalkyl, C1-C6 alkylamino, C1-C6 cycloalkyl, C3-C20 heterocycloalkyl, —COR40, —CO2R40, aryl, or —CONR40R41;
where R30, when present, is selected from hydrogen, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 heterocycloalkyl, aryl, heteroaryl, and arylalkyl, alkylaryl where each occurrence of C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 heterocycloalkyl, aryl, heteroaryl, and arylalkyl, alkylaryl is optionally substituted with halogen, hydroxy, thiol, cyano, amino, nitro, —O—(C1-C6 alkyl), carboxylic acid, ester, amide, carbamate, urea, guanidine; and
where each occurrence of R40 and R41 is independently selected from hydrogen, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 heterocycloalkyl, aryl, heteroaryl, and arylalkyl, alkylaryl where each occurrence of C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C20 cycloalkyl, C3-C20 heterocycloalkyl, aryl, heteroaryl, arylalkyl, or alkylaryl is optionally substituted with halogen, hydroxy, thiol, cyano, amino, nitro, —O—(C1-C6 alkyl), halogen-substituted-O—(C1-C6 alkyl), —O—(C1-C6 aryl), halogen-substituted-O—(C1-C6 aryl), carboxylic acid, ester, amide, carbamate, urea, guanidine, C1-C4 linear or branched alkyl or haloalkyl, or C3-C6 cycloalkyl optionally substituted with a C1-C3 alkyl group or a C6 aryl group;
and provided that the compound does not have a structure given by the formula:

OG Complex Work Unit Chemistry