Class of HDAC inhibitors expands the renal progenitor cells population and improves the rate of recovery from acute kidney injury
View Patent ↗Compounds and compositions are provided that inhibit histone deacylase activity and which expand renal progenitor cell populations and improve kidney function in a damaged kidney. Methods of use of the compounds and compositions are provided.
1. A method of improving kidney function in a patient having acute kidney damage, comprising administering to the patient a compound having the formula:
in which
R is S;
R1 is —OR5 where R5 is H or C 1-4 alkyl;
R2 is phenyl or
where R6 is halo, C 1-4 alkyl, or C 1-4 alkoxy; and
R3 is from 3 to 5 methylene groups ((—CH 2 —) 3-5 ),
or a pharmaceutically acceptable salt thereof in an amount effective to increase renal progenitor cell production in a damaged kidney of the patient.
2. The method of claim 1 , in which the amount effective to increase renal progenitor cell production in the renal cells is an amount effective to reduce blood urea nitrogen (BUN) levels in a patient.
3. The method of claim 1 , in which the amount effective to increase renal progenitor cell production in the renal cells ranges from 0.05 to 200 mg/kg/day.
4. The method of claim 1 , in which the amount effective to increase renal progenitor cell production in the renal cells ranges from 0.05 to 100 mg/kg/day.
5. A method of inhibiting a histone deacetylase in a cell in a patient having acute kidney injury, comprising contacting the cell with a compound having the formula:
in which
R is S;
R1 is —OR5 where R5 is H or C 1-4 alkyl;
R2 is phenyl or
where R6 is halo, C 1-4 alkyl, or C 1-4 alkoxy; and
R3 is from 3 to 5 methylene groups ((—CH 2 —) 3-5 ),
or a pharmaceutically acceptable salt thereof in an amount effective to inhibit a histone deacetylase in the cell.
6. The method of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
7. The method of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
8. The method of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
9. The method of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
11. The method of claim 5 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
12. The method of claim 5 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
13. The method of claim 5 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
14. The method of claim 5 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
15. The method of claim 5 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
16. A method of improving kidney function in a patient having acute kidney damage, comprising administering to the patient a compound having the formula:
in which
R is S;
R1 is —OR5, where R5 is C 1-4 alkyl;
R2 is phenyl or
where R6 is halo, C 1-4 alkyl, or C 1-4 alkoxy and;
R3 is from 3 to 5 methylene groups ((—CH 2 —) 3-5 ),
or a pharmaceutically acceptable salt thereof in an amount effective to increase renal progenitor cell production in a damaged kidney of the patient.