Class of HDAC Inhibitors Expands the Renal Progenitor Cells Population and Improves the Rate of Recovery from Acute Kidney Injury

1 . A compound having the formula:

wherein,

R is S, S(O), S(O) 2 or NH;

R1 is —NHR4 where R4 is OH, aminophenyl, hydroxyphenyl, C 1-4 alkyl hydroxyphenyl or phenyl hydroxyphenyl, or —OR5 where R5 is H or C 1-4 alkyl;

R2 is phenyl; substituted phenyl, where R5 is halo; methyl; C 1-4 alkyl; methoxy; C 1-4 alkoxy; naphthyl; 1H-1,3-benzodiazol-2-yl; 1,3-benzothiazol-2-yl; pyrimidinyl; 1-methyl-1H-1,3benzodiazol-2-yl; pyridyl; methoxyphenyl; or methylthiophenyl; and

R3 is from 0 to 5 methylene groups ((—CH 2 —) 0-5 ) or 0 or 1 phenylene wherein at least one methylene or phenylene is present,

or a pharmaceutically acceptable salt thereof, other than 4-(phenylthio)butanoic acid.

2 . The compound of claim 1 , wherein R is S.

3 . The compound of claim 2 , wherein R3 is —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —, or —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —.

4 . The compound of claim 2 , wherein R2 is phenyl, 4-fluorophenyl, 4-methoxyphenyl, or 4-methylphenyl.

5 . The compound of claim 2 , wherein R3 is —CH 2 —CH 2 —CH 2 — or —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 — and R2 is phenyl, 4-fluorophenyl, 4-methoxyphenyl or 4-methylphenyl.

6 . The compound of claim 2 , wherein R1 is —NH—OH, —NH-2-aminophenyl, -NH-2-hydroxyphenyl, or —O—CH 3 .

7 . The compound of claim 1 , having the formula:

or a pharmaceutically acceptable salt thereof.

8 . The compound of claim 1 , having the formula:

or a pharmaceutically acceptable salt thereof.

9 . The compound of claim 1 , having the formula:

or a pharmaceutically acceptable salt thereof.

10 . The compound of claim 1 , having the formula:

or a pharmaceutically acceptable salt thereof.

11 . The compound of claim 1 , having the formula:

or a pharmaceutically acceptable salt thereof.

12 . A composition comprising a compound having the formula:

wherein,

R is S, S(O), S(O) 2 , or NH;

R1 is —NHR4, where R4 is OH, aminophenyl, hydroxyphenyl, C 1-4 alkyl hydroxyphenyl, phenyl hydroxyphenyl, or —OR5 where R5 is H or C 1-4 alkyl;

R2 is phenyl; substituted phenyl, where R5 is halo; methyl, C 1-4 alkyl; methoxy; C 1-4 alkoxy; naphthyl; 1H-1,3-benzodiazol-2-yl; 1,3-benzothiazol-2-yl; pyrimidinyl; 1-methyl-1H-1,3benzodiazol-2-yl; pyridyl; methoxyphenyl; or methylthiophenyl; and

R3 is from 0 to 5 methylene groups ((—CH 2 -) 0-5 ) or 0 or 1 phenylene wherein at least one methylene or phenylene is present,

or a pharmaceutically acceptable salt thereof, in an amount effective to increase renal progenitor cell production in a kidney of a patient, and a pharmaceutically-acceptable excipient.

13 . The composition of claim 12 , wherein R is S.

14 . The composition of claim 13 , wherein R3 is —CH 2 —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —CH 2 —, or —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —.

15 . The composition of claim 13 , wherein R2 is phenyl, 4-fluorophenyl, 4-methoxyphenyl, or 4-methylphenyl.

16 . The composition of claim 13 , wherein R3 is —CH 2 —CH 2 —CH 2 — or —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 —, and R2 is phenyl, 4-fluorophenyl, 4-methoxyphenyl, or 4-methylphenyl.

17 . The composition of claim 13 , wherein R1 is —NH—OH, —NH-2-aminophenyl, NH-2-hydroxyphenyl, or —O—CH 3 .

18 . The composition of claim 12 , wherein the compound has the formula:

or a pharmaceutically acceptable salt of any of the preceding.

19 . The composition of claim 12 , wherein the compound has the formula:

or a pharmaceutically acceptable salt thereof.

20 . The composition of claim 12 , comprising a cyclodextrin complexed with the compound.