Nrf2 inhibitors and uses thereof
AssigneeBoard of Trustees of Michigan State University
InventorsKaren Liby, Di Zhang, Aaron Odom, Zhilin Hou
Life of this patent
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Abstract
The disclosure relates to compounds of the formulae (I), (II), (lla), (III), (IV), and (IVa) and pharmaceutically acceptable salts, polymorphs, prodrugs, solvates or clathrates thereof, and pharmaceutical compositions comprising such compounds. The disclosure also relates to treating cancer with such compounds and compositions.
Claims70
A compound of the formula (I):
- or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein:
- R1—R6 are each independently H, alkyl, aryl, arylalkyl, OR7, cyano, amino, amido or halo, wherein R7 is H, alkyl, arylalkyl or a protecting group or R4 and R6, together with the atoms to which they are attached, form an aryl or a heteroaryl group;
- X1 is X3, —O—X4—, or —N(R8)—X4—, wherein X3 is alkyl, X4 is a bond or alkyl, and R8 is H, alkyl, arylalkyl or acyl;
- and
- X2 is CR1 or N;
- wherein the compound is not:
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A compound of the formula (III):
- or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein:
- A is aryl or heteroaryl;
- RA is H, alkyl, alkynyl, aryl, arylalkyl, OR7, C(O)OR7, cyano, amino, amido, or halo, wherein R7 is H, alkyl, arylalkyl or a protecting group;
- R2—R6 are each independently H, alkyl, aryl, arylalkyl, OR7, cyano, amino, amido, or halo, wherein R7 is H, alkyl, arylalkyl or a protecting group;
- X1 is X3, —O—X4—, or —N(R8)—X4—, wherein X3 is alkyl (e.g., CH2), X4 is a bond or alkyl, and R8 is H, alkyl, arylalkyl or acyl;
- and
- X2 is CR1 or N.
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A method for treating a tumor with constitutive activation of the Nrf2 pathway, the method comprising administering one or more compounds of the formula (III):
- or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein:
- A is heteroaryl;
- RA is H, alkyl, alkynyl, aryl, arylalkyl, OR7, C(O)OR7, cyano, amino, amido, or halo, wherein R7 is H, alkyl, arylalkyl or a protecting group;
- R2—R6 are each independently H, alkyl, aryl, arylalkyl, OR7, cyano, amino, amido, or halo, wherein R7 is H, alkyl, arylalkyl or a protecting group;
- X1 is X3, —O—X4—, or —N(R8)—X4—, wherein X3 is alkyl (e.g., CH2), X4 is a bond or alkyl, and R8 is H, alkyl, arylalkyl or acyl;
- and
- X2 is CR1 or N;
- or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof.
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Dependencies are inferred from the claim text.