Compounds for the Treatment Of Acute and Chronic Kidney Disease
AssigneesSouthern Research Institute, The UAB Research Foundation, The United States Government as represented by the Department of Veterans Affairs
InventorsMark J. Suto, Bini Mathew, Anupam Agarwal, Amie M. Traylor
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Abstract
The present disclosure is concerned with thioquinolinone compounds for the treatment of disorders associated with heme oxygenase-1 (HO-1) signaling dysfunction such as, for example, kidney diseases (e.g., chronic kidney disease, acute kidney injury). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Claims20
A compound having a structure represented by a formula:
- wherein n is 1 or 2;
- wherein each of R1a, R1b, and R1c is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, provided that at least one of R1a, R1b, and R1c is —OH, C1-C4 alkoxy, or C1-C4 alkylamino;
- wherein each of R2a and R2b is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
- and
- wherein each of R3a, R3b, R3c, R3d, R3e, and R3f is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl,
- provided that at least two of R1a, R1b, R1c, R2a, and R2b are non-hydrogen groups, and provided that when n is 1, Z is —S—, and R1a is —OH or C1-C4 alkoxy, then exactly two of R1a, R1b, R1c, R2a, and R2b are non-hydrogen groups,
- or a pharmaceutically acceptable salt thereof.
A method for treating a disorder associated with heme oxygenase-1 (HO-1) signaling dysfunction in a subject in need thereof, the method comprising administering to the subject an effective amount of compound having a structure represented by a formula:
- wherein n is 1 or 2;
- wherein each of R1a, R1b, and R1c is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, provided that at least one of R1a, R1b, and R1c is —OH, C1-C4 alkoxy, or C1-C4 alkylamino;
- wherein each of R2a and R2b is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
- and
- wherein each of R3a, R3b, R3c, R3d, R3e, and R3f is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl,
- provided that at least two of R1a, R1b, R1c, R2a, and R2b are non-hydrogen groups, and
- provided that when n is 1, Z is —S—, and R1a is —OH or C1-C4 alkoxy, then exactly two of R1a, R1b, R1c, R2a, and R2b are non-hydrogen groups,
- or a pharmaceutically acceptable salt thereof, thereby treating the disorder in the subject.
A method for modifying HO-1 signaling in a subject, the method comprising administering to the subject an effective amount of compound having a structure represented by a formula:
- wherein n is 1 or 2;
- wherein each of R1a, R1b, and R1c is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, provided that at least one of R1a, R1b, and R1c is —OH, C1-C4 alkoxy, or C1-C4 alkylamino;
- wherein each of R2a and R2b is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
- and
- wherein each of R3a, R3b, R3c, R3d, R3e, and R3f is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl,
- or a pharmaceutically acceptable salt thereof, thereby modifying HO-1 signaling in the subject.
Dependencies are inferred from the claim text.