US 12,269,899 B2
Peptidomimetic inhibitors of β-catenin/Tcf protein-protein interaction
Haitao Ji, Tampa, FL (US)
Assigned to H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL (US)
Appl. No. 17/311,623
Filed by H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC., Tampa, FL (US)
PCT Filed Dec. 6, 2019, PCT No. PCT/US2019/064929
§ 371(c)(1), (2) Date Jun. 7, 2021,
PCT Pub. No. WO2020/118179, PCT Pub. Date Jun. 11, 2020.
Claims priority of provisional application 62/776,726, filed on Dec. 7, 2018.
Prior Publication US 2022/0024977 A1, Jan. 27, 2022
Int. Cl. C07K 5/10 (2006.01); A61P 35/00 (2006.01); C07K 5/113 (2006.01); A61K 38/00 (2006.01)
CPC C07K 5/1021 (2013.01) [A61P 35/00 (2018.01); A61K 38/00 (2013.01)] 18 Claims
 
1. A compound having Formula I,

OG Complex Work Unit Chemistry
wherein
X is N—Ra, wherein Ra is selected from hydrogen or C1-C3 alkyl;
Z is selected from O or N—Ra, wherein Ra is selected from hydrogen or C1-C3 alkyl;
R1 is absent or independently for each occurrence, selected from halogen, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, C1-C3 alkoxy, hydroxyl, amino, cyano, nitro, or isocyano;
R2 is C1-C6 alkyl, C3-C10 cycloalkyl, a C2-C8 heterocycloalkyl, C5-C10 aryl, C2-C8 heteroaryl, alkylaryl, alkylheteroaryl, wherein R2 is optionally substituted with halogen, hydroxyl, carboxyl, amino, cyano, nitro, isocyano, alkyl, haloalkyl, haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
R3 and R4 are independently halogen, hydroxyl, amino, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —R′CO2H, —R′CONH2, —R′CONHR″, —R′CONR″R″ “, —R′CO2R”, —R′SO3H, —R′SO2NHCOR″, —R′CONHSO2R″, —R′CONHOH, —R′CONHCN, —R′SO2NHR″, C3-C6 cycloalkyl, C1-C8 heterocycloalkyl, C5-C10 aryl, C1-C8 heteroaryl, wherein R3 and R4 are optionally substituted with halogen, hydroxyl, amino, cyano, nitro, isocyano, carboxyl, hydroxyl, alkyl, alkoxy, alkenyl, haloalkyl, haloalkoxy, cyclopropyl, and wherein R′, R″, and R′″ are independently absent or is hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl;
R5 is C1-C6 alkyl, C1-C6 alkoxy, C3-C8 cycloalkyl, a C1-C7 heterocycloalkyl, C5-C10 aryl, alkylaryl, C1-C8 heteroaryl, alkylheteroaryl, wherein R5 is optionally substituted with halogen, hydroxyl, amino, cyano, nitro, isocyano, carboxyl, hydroxyl, alkyl, alkoxy, alkenyl, haloalkyl, haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
R6 is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, or C1-C3 haloalkyl,
n is 0, 1, 2, 3, or 4;
wherein positions labeled 1, 2, and 3 indicate chiral positions; or
a pharmaceutically acceptable salt or ester thereof.