Indolinyl-sulfonamide inhibitors of tankyrase and methods of use thereof
AssigneeBoard of Regents, The University of Texas System
InventorsLawrence Lum, Chuo Chen, Xuewu Zhang, Ozlem Kulak, Xiaofeng Wu
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Abstract
The present disclosure provides compounds that may be useful for inhibiting the Tankyrase enzyme. In some aspects, these compounds are useful in the treatment of a disease or disorder related to the misregulation of Tankyrase enzyme such as cancer, degenerative diseases, or fibrotic diseases. Also provided herein are compounds may also be used to prevent the elongation of the telomere in a cell.
Claims17
A method of inhibiting a Tankyrase enzyme in a cell comprising administering to the cell an amount sufficient to cause inhibition of a compound of the formula:
- wherein:
- R1 is hydrogen, alkyl(C≤8), substituted alkyl(C≤8), acyl(C≤8), or substituted acyl(C≤8);
- R2, R3, and R4 are each independently selected from hydrogen, amino, cyano, halo, hydroxy, nitro, alkyl(C≤8), substituted alkyl(C≤8), alkoxy(C≤8), substituted alkoxy(C≤8), alkylamino(C≤8), substituted alkylamino(C≤8), dialkylamino(C≤8), substituted dialkylamino(C≤8), amido(C≤8), substituted amido(C≤8), acyl(C≤8), or substituted acyl(C≤8);
- n is 1, 2, 3, or 4;
- A1 and A2 are each independently selected from —C(O)— or —S(O)2—;
- x and y are each independently selected from 1, 2, 3, 4, or 5;
- R5 is hydrogen, alkyl(C≤8), substituted alkyl(C≤8), acyl(C≤8), or substituted acyl(C≤8);
- R6 is aryl(C≤12), heteroaryl(C≤12), or a substituted version of either of these groups;
- or a pharmaceutically acceptable salt thereof.
A method of treating a disease or disorder associated with the misregulation of a Tankyrase enzyme in a patient comprising administering to the patient in need thereof a therapeutically effective amount of a compound or a pharmaceutical composition comprising a compound of the formula:
- wherein:
- R1 is hydrogen, alkyl(C≤8), substituted alkyl(C≤8), acyl(C≤8), or substituted acyl(C≤8);
- R2, R3, and R4 are each independently selected from hydrogen, amino, cyano, halo, hydroxy, nitro, alkyl(C≤8), substituted alkyl(C≤8), alkoxy(C≤8), substituted alkoxy(C≤8), alkylamino(C≤8), substituted alkylamino(C≤8), dialkylamino(C≤8), substituted dialkylamino(C≤8), amido(C≤8), substituted amido(C≤8), acyl(C≤8), or substituted acyl(C≤8);
- n is 1, 2, 3, or 4;
- A1 and A2 are each independently selected from —C(O)— or —S(O)2—;
- x and y are each independently selected from 1, 2, 3, 4, or 5;
- R5 is hydrogen, alkyl(C≤8), substituted alkyl(C≤8), acyl(C≤8), or substituted acyl(C≤8);
- R6 is aryl(C≤12), heteroaryl(C≤12), or a substituted version of either of these groups;
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising an excipient or a pharmaceutically acceptable carrier and a compound of the formula:
- wherein:
- R1 is hydrogen, alkyl(C≤8), substituted alkyl(C≤8), acyl(C≤8), or substituted acyl(C≤8);
- R2, R3, and R4 are each independently selected from hydrogen, amino, cyano, halo, hydroxy, nitro, alkyl(C≤8), substituted alkyl(C≤8), alkoxy(C≤8), substituted alkoxy(C≤8), alkylamino(C≤8), substituted alkylamino(C≤8), dialkylamino(C≤8), substituted dialkylamino(C≤8), amido(C≤8), substituted amido(C≤8), acyl(C≤8), or substituted acyl(C≤8);
- n is 1, 2, 3, or 4;
- A1 and A2 are each independently selected from —C(O)— or —S(O)2—;
- x and y are each independently selected from 1, 2, 3, 4, or 5;
- R5 is hydrogen, alkyl(C≤8), substituted alkyl(C≤8), acyl(C≤8), or substituted acyl(C≤8);
- R6 is aryl(C≤12), heteroaryl(C≤12), or a substituted version of either of these groups;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.