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1. (WO2018039581) USE OF HDAC6 INHIBITORS FOR PREVENTING AND TREATING RENAL CYSTOGENESIS, RENAL CELL CARCINOMA, AND RENAL CILIOPATHIES
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CLAIMS

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A method of treating a renal disease in a subject in need thereof, comprising administering a therapeutically effective amount of a histone deacetylase 6 (HDAC6)-specific inhibitor to the subject, wherein the HDAC6-specific inhibitor is a compound of Formula I


(I)

or a pharmaceutically acceptable salt thereof,

wherein

ring B is aryl or heteroaryl;

Ri is an aryl or heteroaryl, each of which may be optionally substituted by OH, halo, or Ci-6-alkyl; and

R is H or Ci-6-alkyl.

2. The method of Claim 1, wherein the compound of Formula I is:


or a pharmaceutically acceptable salt thereof.

3. A method of treating a renal disease in a subject associated with high histone deacetylase 6 (FIDAC6) signaling, comprising administering a therapeutically effective amount of an FIDAC6-specific inhibitor to the subject, wherein the FIDAC6-specific inhibitor is a compound of Formula I


(I)

or a pharmaceutically acceptable salt thereof,

wherein

ring B is aryl or heteroaryl;

Ri is an aryl or heteroaryl, each of which may be optionally substituted by OH, halo, or Ci-6-alkyl; and

R is H or Ci-6-alkyl.

4. The method of Claim 3, wherein the compound of Formula I is:


or a pharmaceutically acceptable salt thereof.

5. A method of treating a renal disease in a subject associated with high aurora kinase A (AURKA)- histone deacetylase 6 (HDAC6) signaling, comprising administering a therapeutically effective amount of a combination of an HDAC6-specific inhibitor and an AURKA inhibitor to the subject, wherein the HDAC6-specific inhibitor is a compound of Formula I


(I)

or a pharmaceutically acceptable salt thereof,

wherein

ring B is aryl or heteroaryl;

Ri is an aryl or heteroaryl, each of which may be optionally substituted by OH, halo, or Ci-6-alkyl; and

R is H or Ci-6-alkyl.

6. The method of Claim 5, wherein the compound of Formula I is:


or a pharmaceutically acceptable salt thereof.

7. The method of any one of Claims 1-6, wherein the renal disease is, or is associated with, ciliopathy, Von Hippel-Lindau (VHL) disease, renal cystogenesis, renal cell carcinoma, and Tuberous Sclerosis Complex (TSC).

8. The method of any one of Claims 1-7, wherein the renal disease is renal cystogenesis.

9. The method of any one of Claims 1-8, wherein the HDAC6-specific inhibitor directly inhibits the activity of HDAC6.

10. The method of any one of Claims 1-9, wherein the subject is a mammal.

11. The method of any one of Claims 1-10, wherein the subject is a human, mouse, or rat.