Substituted pyrrolidones and piperidones as small molecule inhibitors of EZH2 and EED protein binding
AssigneeNorthwestern University
InventorsGary E. Schiltz, Jindan Yu
Life of this patent
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Abstract
Disclosed are substituted pyrrolidones and piperidones which may be utilized as EZH2 targeting agents. The substituted pyrrolidones and piperidones may include substituted 2-pyrrolidones and 2-piperidones. The disclosed pyrrolidones and piperidones may be used in pharmaceutical compositions and methods for treating cell proliferative disorders such as cancer.
Claims20
A method of inhibiting the growth of cells that express EZH2 protein in a subject in need thereof, the method comprising administering a compound having a formula I, or a pharmaceutically acceptable salt thereof,
- wherein
- m is 0-2, n is 0-1, and p is 0-1, with the proviso that (m+n+p) is 2 or 3;
- A is —C(R1)(R2)—;
- X is selected from —N(R3)—C(O)—, —N(R3)—CH2—, —CH2—N(R3)—C(O)—, —N(R3)—C(O)—CH2—, —N(R3)—, —N(R3)—S(O)(O)—, and —C(O)—N(R3)—;
- R1, R2, and R3 are independently selected from hydrogen and alkyl;
- and
- R and R′ are independently selected from cycloalkyl, heterocycloalkyl, alkyl (heterocycloalkyl), aryl, heteroaryl, alkyl (aryl), and alkyl(heteroaryl), and R and R′ optionally are substituted at one or more positions with a substituent selected from alkyl, alkoxy, halogen, haloalkyl, amino, cyano, nitro, aryl, hydroxyl, carboxyl, carboxy (alkyl) ester, acyl, and oxo.
A method of inhibiting binding of the EZH2 protein in the PRC2 complex in a subject in need thereof, the method comprising administering a compound having a formula I, or a pharmaceutically acceptable salt thereof,
- wherein
- m is 0-2, n is 0-1, and p is 0-1, with the proviso that (m+n+p) is 2 or 3;
- A is —C(R1)(R2)—;
- X is selected from —N(R3)—C(O)—, —N(R3)—CH2—, —CH2—N(R3)—C(O)—, —N(R3)—C(O)—CH2—, —N(R3)—, —N(R3)—S(O)(O)—, and —C(O)—N(R3)—;
- R1, R2, and R3 are independently selected from hydrogen and alkyl;
- and
- R and R′ are independently selected from cycloalkyl, heterocycloalkyl, alkyl(heterocycloalkyl), aryl, heteroaryl, alkyl(aryl), and alkyl(heteroaryl), and R and R′ optionally are substituted at one or more positions with a substituent selected from alkyl, alkoxy, halogen, haloalkyl, amino, cyano, nitro, aryl, hydroxyl, carboxyl, carboxy (alkyl) ester, acyl, and oxo.
Dependencies are inferred from the claim text.